WO2019195941A1

WO2019195941A1 - Dna methylation assays and methods

Info

Publication number: WO2019195941A1
Application number: PCT/CA2019/050444
Authority: WO
Inventors: Bekim SADIKOVIC; Erfan AREF ESHGHI
Original assignee: London Health Sciences Centre Research Inc.
Priority date: 2018-04-13
Filing date: 2019-04-12
Publication date: 2019-10-17

Abstract

A method for diagnosing prostate cancer in a subject, the method comprises measuring the methylation level of at least one CpG locus in a sample from the subject, wherein the at least one CpG locus is selected from the loci listed in Table 1 and/or is within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides of at least one of the loci listed in Table 1; and determining the level of similarity between the measured methylation level and a predefined level indicative of prostate cancer, wherein a high degree of similarity between the measured methylation level and the predefined level indicates the presence or increased likelihood of prostate cancer.

Description

DNA Methylation Assays and Methods

Field

The present invention relates to DNA methylation. More specifically, the present invention is, in aspects, concerned with methods and assays for detecting DNA methylation.

Background

Prostatic adenocarcinoma is the most commonly diagnosed non-cutaneous cancer for men in the United States. The incidence is likely to continue to increase as people survive longer and more middle-aged men undergo routine screening for the disease. Men diagnosed with early stage small volume disease have the best outcome following curative treatment. Therefore the aim of early detection programs is to diagnose cancer at an early curable stage.

The gold standard for diagnosis currently entails digital rectal exam and measurement of serum prostate-specific antigen (PSA) and if either is suspicious it is followed by trans-rectal prostatic needle biopsy. However, serum PSA can be elevated in benign conditions and needle biopsy may fail to identify even significant amounts of cancer due to sampling error and

morphological heterogeneity of the tumor. Therefore, the introduction of additional diagnostic tests is needed to improve the sensitivity of prostate cancer diagnosis.

DNA methylation is a process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts to repress gene transcription. DNA methylation is essential for normal development and is associated with a number of key processes including genomic imprinting, X-chromosome inactivation, repression of transposable elements, aging, and carcinogenesis.

Goh et al. (PloS One 2014;9(3):e91666) aimed to identify a prostate cancer DNA

hypermethylation microarray signature (denoted as PHYMA) that differentiates prostate cancer from benign prostate hyperplasia (BPH), high from low-grade and lethal from non-lethal cancers. A classification model was generated, consisting of a 55-probe DNA methylation signature of 46 genes. The model was independently validated on an internal testing dataset.

Kirby et al. (BMC cancer 2017; 17(1 ):273) measured genome-wide DNA methylation patterns in 73 clinically annotated fresh-frozen prostate cancers and 63 benign-adjacent prostate tissues using the lllumina Infinium HumanMethylation450 BeadChip array and identified methylation patterns that have a high predictive power for distinguishing malignant prostate tissue from benign- adjacent prostate tissue. It was found that DNA methylation patterns are greatly altered in prostate cancer tissue in comparison to benign adjacent tissue and can distinguish prostate cancers with high specificity and sensitivity in multiple patient tissue cohorts.

U.S. Patent Application Publication No. 2003/0215842 describes a method for the systematic identification of differentially methylated CpG dinucleotides positions within genomic DNA sequences for use as reliable diagnostic, prognostic and/or staging markers. Particular embodiments comprise genome-wide identification of differentially methylated CpG dinucleotide sequences, further identification of neighboring differentially methylated CpG dinucleotide sequences, and confirmation of the diagnostic utility of selected differentially methylated CpG dinucleotide among a larger set of diseased and normal biological samples. The method, and kits for implementation thereof, are useful in applied assays for the diagnosis, prognosis and/or staging of conditions characterized by differential methylation.

International Patent Application Publication No. 2016/115530 describes methods, systems, platforms, non-transitory computer-readable medium, services, and kits for determining a cancer type in an individual. Also described herein include methods, systems, platforms, non-transitory computer-readable medium, and compositions for generating a CpG methylation profile database.

International Patent Application Publication No. 2017/048932 describes methods for the detection and diagnosis of cancer. In one aspect, described are methods for detecting the presence of cancer in an individual by detecting the methylation state of a region in the promoter of the ZNF154 gene. Methods are described for detection and diagnosis of cancer from circulating tumor DNA which are minimally invasive and have diagnostic utility across different types and sub-types of cancer. In a further aspect, bioinformatics methods are described to analyze the methylation state of the ZNF154 promoter and relate the methylation state to the likelihood of cancer in the individual.

The ConfirmMDx test is highly sensitive for DNA hypermethylation of GSTP1 , APC and RASSF1 in the tissue surrounding a prostate cancer (https://mdxhealth.com/press- release/mdxhealths-confirmmdx-genes-identify-prostate-cancer-aggressiveness-diagnostic).

There is a need for alternative methods and assays that overcome or mitigate at least some of the deficiencies of the prior art, and/or to provide a useful alternative.

Description of the Drawings

The present invention will be further understood from the following description with reference to the Figures, in which:

Figure 1 shows differentially methylated CpGs in Pea with a volcano plot of the comparison between the tumors and benign samples: X-axis: methylation difference (mean tumor - mean normal); Y-axis: negative logarithmic scale of p-value; vertical dashed lines: methylation difference cut-off (0.2); horizontal line: p-value cut-off (0.01 , Bonferroni-corrected). The significant probes are shown in red.

Figure 2 shows differentially methylated CpGs in Pea with a heatmap of the tumors

(columns, blue bar) and the adjacent benign tissues (columns, red bar) using 6,167 differentially methylated loci (rows): intensity of blue color corresponds to the methylation levels. Numbers bellow columns: proportion of tumor cellularity.

Figure 3 shows the average methylation levels of the identified probes across the samples (Y-axis) are highly correlated with the level of tumor cellularity (X-axis). Correlation coefficient: 0.92

(p<0.0001).

Figure 4 shows gene-set enrichment analysis of differentially methylated CpGs in PCa with multiple dimensional scaling of the GO terms (circles): GO terms with closely related functionalities are clustered in groups. Circles with smaller distance from each other represent GO terms with similar functionality. The uniqueness of every GO term is shown using a color scale from blue (less unique) to red (more unique). Representative non-redundant GO terms from every cluster are written next to the related circles. Only 350 of the GO terms were selected by REVIGO for reduction and visualization (maximum software limit).

Figure 5 shows gene-set enrichment analysis of differentially methylated CpGs in PCa with hierarchical relationship between the significant GO terms: the level of significance (p-value) of every functional category is illustrated by a color scale from white to red.

Figure 6 shows protein interaction analysis of differentially methylated genes: The DNA methylation protein interactome of the analyzed genes are composed of a complex network of nodes (proteins encoded by genes) and edges (connecting lines). The edge weight is composed of the combined absolute values of the differential methylation statistics of the probes in the promoters of the two interacting genes. Within this complex network, nine sub-networks with at least ten genes were found to have an average edge weight (modularity) higher than that observed in 1 ,000 random permutations (FDR<0.01). The modularity scores of these nine hotspots (EpiMods) are presented as a bar plot on the top left. Among these, two EpiMods are visualized (COL3A1 and ITGA4, bottom left and top right). Red and blue nodes represent hyper- and hypo-methylation of the gene promoters, respectively. The white nodes represent genes with no methylation change (details in Table 3 and Table 4).

Figure 7 shows a correlation between CNV status and DNA methylation in PCa:

Hypermethylation in the promoter of the CLIP4 gene partially correlates with its CNV status. The figure illustrates a segment in the promoter of CLIP4 gene, located in the short arm of chromosome 2. The region is marked with high levels of acetylation of the 27^th lysine residue of Histone 3, (H3K27Ac), a maker associated with active promoters. The segment is also recognized as a CpG island (green pane). Panels A and B represent 181 base-pairs of this segment, harboring a total of 8 CpG probes which were identified to concurrently show both hypermethylation and CNV amplification. A) The color scale of the vertical bars (each probe) represents the log ratios of the copy numbers. The color scale above 0.2 is shown with red and indicates a minimum of one copy amplification for the region. Color scales of white and light blue represent no CNV change (we defined a CNV loss with a log ratio < -0.3, which is not observed for this region). Samples are sorted from top to bottom. The top 16 samples represent normal tissues and the lower samples indicate the tumors (vertical pane as an indicator: blue and pink). Within this segment, the right five probes show CNV amplification in tumors, but not in the adjacent benign tissues. B) The methylation status of the same eight probes shows a hypermethylation in tumors (pink) relative to normal adjacent benign tissues (blue). Methylation level of every probe from every sample is presented with a dot, representing a methylation range between 0 and 1 (bottom to top). Lines represent mean, and shadows around the lines indicate 95% confidence intervals of the mean in every group. The region with CNV amplification is significantly hypermethylated; however, this hypermethylation extends beyond the CNV to three probes in the upstream.

Figure 8 shows motifs enriched within ±5kb of differentially methylated regions: TF:

Transcription factor; N. Pos.: Number of observed motifs; Expected: Number of expected motifs; Enrichment: Fold enrichment; P-value is corrected for multiple testing using Bonferroni method. Motifs are sorted by fold enrichment.

Figure 9 shows a prediction algorithm for classification of prostate samples: A) Four CpG probes selected by LASSO for training the classification model show significant hypermethylation in the tumors as compared to the normal samples. Y-axis represent the methylation levels. B) The classification model yields 100% accuracy (AUC=1.00) in the training dataset and 97% accuracy (AUC=0.98) in the validating dataset of 92 benign samples and 234 tumors (model details in Table 7 and Table 8); C) Classification scores generated by the model for 16 normal samples in the training dataset (Benign T), 31 tumor samples in the training dataset (Tumor T), 76 benign tissue from validating dataset (Benign V), 234 tumors from validating dataset (Tumor V), 6 normal radical prostatectomy from validating dataset (Normal RP), 10 benign prostate hyperplasia (BPH) from validating dataset, 6 PCa metastasis from bone, lymph node, and soft tissue (Metastasis), as well as 61 tumor technical replicates are shown using violin-jitter plots. Y-axis represents the tumor probability scores (0-1), stratified by different classes in the X-axis. Violin-jitter plots show the density and distributions of the scores in every category. The normal samples mostly receive a score between 0.15 and 0.45, while the majority of the tumors are scored >0.65. The default cut-off of 0.5 (dashed line) is used for classification. Only two of the normal samples out of 92 received a score similar to other tumors, and only 9 misclassifications out of 234 have been made for tumors. Technical replicates have also generated comparable scores to the samples in the main tumor category. Figure 10 shows hypermethylation of APC promoter in 31 prostate cancer FFPE tissues as compared with 16 normal tissues. The figure illustrates a 422 base-pair region, containing 15 probes with an average methylation difference of 29% between the two groups (family-wise error rate after 1 ,000 permutations < 0.0001), overlapping 5’UTR, first exon and first intron of APC gene. Track one: Chromosome Ideogram; Track two: CpG probes; Track 3: Gene region; Track Four: Methylation level data; Pink: Tumor; Blue: Normal; Line: average methylation; Shadow: 95% confidence interval; Dots: methylation values from every single sample (0-1).

Summary

In accordance with an aspect, there is provided a method for diagnosing prostate cancer in a subject, the method comprising:

measuring the methylation level of at least one CpG locus in a sample from the subject, wherein the at least one CpG locus is selected from the loci listed in Table 1 and/or is within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides of at least one of the loci listed in Table 1 ; and

determining the level of similarity between the measured methylation level and a predefined level indicative of prostate cancer, wherein a high degree of similarity between the measured methylation level and the predefined level indicates the presence or increased likelihood of prostate cancer.

In accordance with an aspect, there is provided a method for distinguishing a malignant from a benign prostate lesion in a subject, the method comprising:

determining the level of similarity between the measured methylation level and a predefined level indicative of a malignant lesion, wherein a high degree of similarity between the measured methylation level and the predefined level indicates the presence or increased likelihood of a malignant lesion.

In accordance with an aspect, there is provided a method for predicting tumor cellularity, the method comprising:

measuring the methylation level of at least one CpG locus in a tumor sample from the subject, wherein the at least one CpG locus is selected from the loci listed in Table 1 and/or is within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides of at least one of the loci listed in Table 1 , wherein the degree of methylation of the at least one CpG locus correlates with the level of tumor cellularity.

In accordance with an aspect, there is provided a method for detecting metastatic prostate lesions, the method comprising:

determining the level of similarity between the measured methylation level and a predefined level indicative of prostate cancer, wherein a high degree of similarity between the measured methylation level and the predefined level indicates the presence or increased likelihood of a metastatic lesion.

In an aspect, the sample is from a suspected metastatic site such as bone, lymph node, or soft tissue.

In an aspect, the at least one CpG locus comprises 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13,

14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 , 32, 33, 34, 35, 36, 37, 38, 39,

40, 41 , 42, 43, 44, 45, 46, 47, 48, 49, 50, 51 , 52, 53, 54, 55, 56, 57, 58, 59, 60, 61 , 62, 63, 64, 65,

66, 67, 68, 69, 70, 71 , 72, 73, 74, 75, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85, 86, 87, 88, 89, 90, 91 ,

92, 93, 94, 95, 96, 97, 98, 99, 100, or more CpG loci.

In an aspect, the at least one CpG locus comprises one or more of eg 13914893,

cg08857201 , cg04207084, cg07858113, cg09706021 , cg19640166, cg21264055, cg01799653, cg05326023, cg02022733, and loci within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides thereof.

In an aspect, at least one CpG locus comprises one or more of cg13914893, cg08857201 , cg04207084, cg07858113, and loci within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides thereof.

In an aspect, the at least one CpG locus comprises cg13914893, cg08857201 , cg04207084, and cg07858113, or loci within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides thereof.

In an aspect, the at least one CpG locus consists of cg13914893, cg08857201 ,

cg04207084, and cg07858113, or loci within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides thereof.

In an aspect, the sample is a prostate biopsy sample.

In an aspect, the sample is a needle biopsy sample.

In an aspect, the sample is a blood sample.

In an aspect, the sample is a urine sample. In accordance with an aspect, there is provided an assay comprising a probe for detecting the DNA methylation status of at least one CpG locus in a sample, wherein the at least one CpG locus is selected from the loci listed in Table 1 and/or is within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides of at least one of the loci listed in Table 1.

92, 93, 94, 95, 96, 97, 98, 99, 100, or more CpG loci.

In an aspect, the at least one CpG locus comprises one or more of eg 13914893,

cg08857201 , cg04207084, cg07858113, and loci within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides thereof.

In an aspect, the at least one CpG locus consists of cg13914893, cg08857201 ,

In an aspect, the assay is for diagnosing prostate cancer and/or identifying a prostate cancer metastatic lesion.

In an aspect, the assay is for distinguishing between malignant and benign prostate lesions.

In an aspect, the assay is a high throughput, low cost assay.

In accordance with an aspect, there is provided a method for detecting the DNA methylation status of at least one CpG locus in a sample, the method comprising contacting the sample with the assay described herein.

In an aspect, the sample is a prostate biopsy sample.

In an aspect, the sample is a needle biopsy sample.

In an aspect, the sample is a blood sample.

In an aspect, the sample is a urine sample.

In an aspect, the sample is from a site of suspected metastasis, such as from bone, lymph node, or soft tissue. In accordance with an aspect, there is provided a method for treating prostate cancer, the method comprising diagnosing the prostate cancer according to the method described herein or using the assay described herein and, upon a positive diagnosis of prostate cancer, treating the prostate cancer.

Other features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples while indicating embodiments of the invention are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from the detailed description.

Detailed Description

Described herein are a number of CpG loci that have been identified as being differentially methylated in prostate cancer specimens as compared to normal tissue. These loci are listed in Table 1 and are described in detail below in Example 1. An algorithm has been trained as described herein to choose a small cohort of probes from Table 1 that collectively provide a reliable model for diagnosing prostate cancer from a biopsy sample.

As described below, the method used to train the algorithm relies on regularization of linear models, using two type of regularization: LASSO and Ridge. In LASSO the coefficients of probes are penalized until they hit zero and drop out of the model. In Ridge the coefficients are penalized until they become very close to zero, but they never hit zero, so no probe will be dropped out. There is a third type of regularization, called elastic net, which is a combination of the previous two. By choosing how much LASSO and how much Ridge regularization is desired (ranging 0-1), the number of probes to be included in the final model can be adjusted. In addition, some probes can be manually removed before any of these procedures.

Using this algorithm permits a high-throughput and low cost assay for diagnosing prostate cancer. The methylation profile of certain CpG loci is measured in the sample and the resulting values are compared to control values for those loci. This provides an immediate“yes” or“no” diagnosis with no preliminary requirement for staining or visual scoring by a skilled worker.

Definitions

Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. See, e.g. Singleton et al., Dictionary of Microbiology and Molecular Biology 2nd ed., J. Wiley &

Sons (New York, N.Y. 1994); Sambrook et al., Molecular Cloning. A Laboratory Manual, Cold Springs Harbor Press (Cold Springs Harbor, NY 1989), each of which are incorporated herein by reference. For the purposes herein, the following terms are defined below. As used herein, "methylation" refers specifically to DNA methylation, and more particularly to a modification in which a methyl group or hydroxymethyl group is added to the 5 position of a cytosine residue to form a 5-methyl cytosine (5-mCyt) or 5-hydroxymethylcytosine (5-hmC).

As used herein, "CpG locus" or "methylation locus" refers to an individual CpG dinucleotide sequence in genomic DNA which is capable of being methylated. Individual CpG loci may be identified by reference to a probe ID, which is defined by a chromosome number and genomic coordinate to unambiguously define each CpG locus.

The term "methylation level" refers to a measure of the amount of methylation at a target site (for example, a CpG locus) within a DNA molecule in a sample. For example, the level of methylation can be measured for one or more CpG dinucleotides, or for a region of DNA. If the methylation level of a target site within a sample is higher than a reference level, the sample is considered to have increased methylation relative to the reference at the target site. Conversely, if the methylation level of a target site within a sample is lower than the reference level, the sample is considered to have a decreased methylation level relative to the reference at the target site. The target site may be an individual CpG locus or a region of DNA comprising multiple CpG loci, for example, a gene promoter. Methylation levels of a target site may be measured by methods known in the art, for example, as a "b value" or "beta value", which is calculated as: b value = intensity of the methylated target

(intensity of the unmethylated target + intensity of the methylated target + 100)

A b value of zero indicates no methylation and a value of one indicates 100% methylation.

As used herein, the term "methylation status" refers to whether a specified target DNA site is methylated or not methylated. The target site may be an individual CpG locus or a region of DNA comprising multiple CpG loci, for example, a gene promoter. For example, a target site may have a methylation status of "methylated" or "hypermethylated" if the target has a significantly higher methylation beta value in a prostate cancer specific control profile compared to a non-prostate cancer control profile. Conversely, a target site may have a methylation status of "not methylated" or "hypomethylated" if the target has a significantly lower methylation beta value in a prostate cancer specific control profile compared to a non-prostate cancer control profile.

As used herein the term "gene" refers to a genomic DNA sequence that comprises a coding sequence associated with the production of a polypeptide or polynucleotide product (e.g., rRNA, tRNA). The methylation level of a gene as used herein, encompasses the methylation level of sequences which are known or predicted to affect expression of the gene, including the promoter, enhancer, and transcription factor binding sites. As used herein, the term "enhancer" refers to a as- acting region of DNA that is located up to 1 Mbp (upstream or downstream) of a gene. As used herein, the term "sample methylation profile" or "sample profile" refers to the methylation levels at one or more target sequences in a subject's genomic DNA. The target sequence may be an individual CpG locus or a region of DNA comprising multiple CpG loci, for example, a gene promoter or CpG island. The methylation profile of a sample tested according the methods disclosed herein is referred to as a sample profile.

In some embodiments, the sample methylation profile is compared to one or more control profiles. The control profile may be a reference value and/or may be derived from one or more samples, optionally from historical methylation data for a patient or pool of patients who are known to have, or not have, prostate cancer. In such cases, the historical methylation data can be a value that is continually updated as further samples are collected and individuals are identified as prostate cancer or not-prostate cancer. It will be understood that the control profile represents an average of the methylation levels for selected CpG loci as described herein. Average methylation values may, for example, be the mean values or median values.

For example, a "prostate cancer specific control profile" or "prostate cancer control profile" may be generated by measuring the methylation levels at specified target sequences in genomic DNA from an individual subject, or population of subjects, who are known to have prostate cancer. Similarly, a "non-prostate cancer control profile" may be generated by measuring the methylation levels at specified target sequences in genomic DNA from an individual subject or population of subjects who are known to not have prostate cancer.

In certain embodiments, the tissue source from which the sample profile and control profile are derived is matched, so that they are both derived from the same or similar tissue.

As used herein, the phrase "detecting and/or screening" for a condition refers to a method or process of determining if a subject has or does not have said condition. Where the condition is a likelihood or risk for a disease or disorder, the phrase "detecting and/or screening" will be understood to refer to a method or process of determining if a subject is at an increased or decreased likelihood for the disease or disorder.

As used herein, the term "sensitivity" refers to the ability of the test to correctly identify those patients with the disease or disorder, such that a 100% sensitivity indicates a test that correctly identifies all patients with the disease or disorder. Sensitivity is calculated as:

Sensitivity = (True Positives)/(True Positives + False Negatives).

A high sensitivity as used herein refers to a sensitivity of greater than 50%.

As used herein, the term "specificity" refers to the ability of a test to correctly identify those patients without the disease or disorder, such that a 100% specificity indicates a test that correctly identifies all patients without the disease or disorder. Specificity is calculated as: Specificity = (True Negatives)/(True Negatives + False Positives).

A high specificity as used herein refers to a specificity of greater than 50%.

As used herein, the term "CpG" or "CG" site refers to cytosine and guanosine residues located sequentially (5' 3') in a polynucleotide DNA sequence. The term "CpG island" refers to a region of genomic DNA characterized by a high frequency of CpG sites, for example, a CpG island may be characterized by CpG dinucleotide content of at least 60% over the length of the island. As used herein the term "CpG island shore" refers to a region of DNA occurring within 2kbp (upstream or downstream) of a CpG island. As used herein the term "body" (in reference to a gene) refers to the genomic region covering the entire gene from the transcription start site to the end of the transcript. As used herein the term "distance from TSS" refers to the genomic difference in base pairs between specific CpG locus and the nearest transcription start site.

As used herein, a first CpG locus is "associated" with a second CpG locus, if the methylation status at the first locus is reasonably predictive of the methylation status of the second locus and vice versa. CpG loci may be considered "associated", for example, if they occur within the same CpG island, CpG island shore, gene promoter or gene enhancer region. CpG loci may also be considered "associated" by virtue of their genomic proximity, for example, CpG loci residing within 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides of each other may be considered associated.

The term "oligonucleotide" as used herein refers to a nucleic acid substantially free of cellular material or culture medium when produced by recombinant DNA techniques, or chemical precursors, or other chemicals when chemically synthesized. The term "nucleic acid" and/or "oligonucleotide" as used herein refers to a sequence of nucleotide or nucleoside monomers consisting of naturally occurring bases, sugars, and intersugar (backbone) linkages, and is intended to include DNA and RNA which can be either double stranded or single stranded, represent the sense or antisense strand. The term also includes modified or substituted oligomers comprising non-naturally occurring monomers or portions thereof.

"Isolated" or "purified" when used in relation to a DNA molecule refers to a DNA molecule that is extracted and separated from one or more contaminants with which it naturally occurs.

As used herein, "treatment" or“therapy” is an approach for obtaining beneficial or desired clinical results. For the purposes described herein, beneficial or desired clinical results include, but are not limited to, alleviation of symptoms, diminishment of extent of disease, stabilized (i.e. , not worsening) state of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, and remission (whether partial or total), whether detectable or undetectable. "Treatment" and“therapy” can also mean prolonging survival as compared to expected survival if not receiving treatment or therapy. Thus, "treatment" or“therapy” is an intervention performed with the intention of altering the pathology of a disorder. Specifically, the treatment or therapy may directly prevent, slow down or otherwise decrease the pathology of a disease or disorder such as an infection, or may render the infection more susceptible to treatment or therapy by other therapeutic agents.

The term "subject" as used herein refers to any member of the animal kingdom, including birds, fish, invertebrates, amphibians, mammals, and reptiles. Typically, the subject is a human or non-human vertebrate. Non-human vertebrates include livestock animals, companion animals, and laboratory animals. Non-human subjects also specifically include non-human primates as well as rodents. Non-human subjects also specifically include, without limitation, poultry, chickens, horses, cows, pigs, goats, dogs, cats, guinea pigs, hamsters, mink, rabbits, crustaceans, and molluscs. Typically the subject is poultry or a mammal. The term "mammal" refers to any animal classified as a mammal, including humans, other higher primates, domestic and farm animals, and zoo, sports, or pet animals, such as dogs, cats, cattle, horses, sheep, pigs, goats, rabbits, etc. Typically, the mammal is human.

In understanding the scope of the present application, the articles“a”,“an”,“the”, and“said” are intended to mean that there are one or more of the elements. Additionally, the term "comprising" and its derivatives, as used herein, are intended to be open ended terms that specify the presence of the stated features, elements, components, groups, integers, and/or steps, but do not exclude the presence of other unstated features, elements, components, groups, integers and/or steps. The foregoing also applies to words having similar meanings such as the terms, "including", "having" and their derivatives.

It will be understood that any aspects described as“comprising” certain components may also“consist of” or“consist essentially of,” wherein“consisting of” has a closed-ended or restrictive meaning and“consisting essentially of’ means including the components specified but excluding other components except for materials present as impurities, unavoidable materials present as a result of processes used to provide the components, and components added for a purpose other than achieving the technical effect of the invention. For example, a composition defined using the phrase“consisting essentially of” encompasses any known pharmaceutically acceptable additive, excipient, diluent, carrier, and the like. Typically, a composition consisting essentially of a set of components will comprise less than 5% by weight, typically less than 3% by weight, more typically less than 1% by weight of non-specified components.

It will be understood that any component defined herein as being included may be explicitly excluded from the claimed invention by way of proviso or negative limitation. For example, in aspects, enteric infections, such as enteric bacterial and/or enteric viral infections, are explicitly excluded from the compositions and methods described herein. In other aspects, the molecules described herein are not bacteriocins. In addition, all ranges given herein include the end of the ranges and also any intermediate range points, whether explicitly stated or not.

Finally, terms of degree such as "substantially", "about" and "approximately" as used herein mean a reasonable amount of deviation of the modified term such that the end result is not significantly changed. These terms of degree should be construed as including a deviation of at least ±5% of the modified term if this deviation would not negate the meaning of the word it modifies.

Assays

Described herein is an assay comprising a probe for detecting the DNA methylation status of at least one CpG locus in a sample. The at least one CpG locus that is detected with the probe is found in Table 1. Alternatively, the CpG locus is a locus associated with one listed in Table 1 and is within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides of the listed locus.

Typically, the assay detects more than one CpG locus, such as 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10,

11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 , 32, 33, 34, 35, 36,

37, 38, 39, 40, 41 , 42, 43, 44, 45, 46, 47, 48, 49, 50, 51 , 52, 53, 54, 55, 56, 57, 58, 59, 60, 61 , 62,

63, 64, 65, 66, 67, 68, 69, 70, 71 , 72, 73, 74, 75, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85, 86, 87, 88,

89, 90, 91 , 92, 93, 94, 95, 96, 97, 98, 99, 100, or more CpG loci. Typically, the assay detects up to about 10 CpG loci, such as 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10. Typically, the assay detects at least 4 CpG loci, such as from about 4 to about 10, such as 4.

As noted above, the CpG loci measured in the assay may comprise any one or more loci listed in Table 1 , or associate loci. Typically, at least one of the following loci are measured:

eg 13914893, cg08857201 , cg04207084, cg07858113, cg09706021 , cg19640166, cg21264055, cg01799653, cg05326023, cg02022733, and loci within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides thereof. Any combinations of these may be measured, from a single loci up to all 10 loci, and any individual locus or combinations of these loci may be measured in combination with additional loci from Table 1 or other loci indicative of prostate cancer and/or tumor cellularity.

More typically, at least one of the following loci are measured: cg13914893, cg08857201 , cg04207084, cg07858113, and loci within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides thereof. Typically, a combination of at least four loci are measured, including at least cg13914893, cg08857201 , cg04207084, and cg07858113 (or loci within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides thereof). In aspects, only four loci are measured, which can be selected from Table 1. However, in such aspects typically cg13914893, cg08857201 , cg04207084, and cg07858113 are measured (or loci within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides thereof). In typical aspects, the assay is used for diagnosing prostate cancer, for classifying prostate cancers by grade, for distinguishing between malignant and benign prostate lesions, for screening for prostate cancer, for determining tumor cellularity, and/or for guiding decisions in subsequent treatment of a detected prostate cancer.

The assay may be used with any type of sample, but typically the sample is a prostate biopsy sample or, more specifically, a needle biopsy sample. The sample may also be a sample from a site suspected of prostate cancer metastasis, such as bone, lymph node, and/or soft tissue. In other aspects, the sample is a blood sample, which may contain circulating tumor cells. The sample may also in aspects be a urine sample.

Advantageously, this assay provides for a high-throughput, low cost method for reliably screening for prostate cancer.

Methods

Described herein is a method for diagnosing, detecting, and/or screening for prostate cancer in a subject. The method comprises measuring the methylation level of at least one CpG locus in a sample from the subject, wherein the at least one CpG locus is selected from the loci listed in Table 1 and/or is within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides of at least one of the loci listed in Table 1. Subsequently, the level of similarity between the measured methylation level and a predefined level indicative of prostate cancer is determined. If there is a high degree of similarity between the measured methylation level and the predefined level, this indicates the presence or increased likelihood of prostate cancer in the subject.

Further described herein is a method for distinguishing a malignant from a benign prostate lesion in a subject. The method comprises measuring the methylation level of at least one CpG locus in a sample from the subject, wherein the at least one CpG locus is selected from the loci listed in Table 1 and/or is within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides of at least one of the loci listed in Table 1. The level of similarity between the measured methylation level and a predefined level indicative of a malignant lesion is determined. If there is a high degree of similarity between the measured methylation level and the predefined level, this indicates the presence or increased likelihood of a malignant lesion.

Further described herein is a method for predicting tumor cellularity. This not only determines whether a tumor is present but further predicts how much tumor is there. The methods comprises measuring the methylation level of at least one CpG locus in a tumor sample from the subject, wherein the at least one CpG locus is selected from the loci listed in Table 1 and/or is within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides of at least one of the loci listed in Table 1. In this aspect, the degree of methylation of the at least one CpG locus correlates with the level of tumor cellularity. Additionally, a method for detecting metastatic prostate lesions is provided. The method comprises measuring the methylation level of at least one CpG locus in a sample from a subject, wherein the at least one CpG locus is selected from the loci listed in Table 1 and/or is within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides of at least one of the loci listed in Table 1. The level of similarity between the measured methylation level and a predefined level indicative of prostate cancer is determined, wherein a high degree of similarity between the measured methylation level and the predefined level indicates the presence or increased likelihood of a metastatic lesion. Typically, the sample is from a suspected metastatic site such as bone, lymph node, or soft tissue.

Typically, these methods detect more the one CpG locus, such as 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10,

89, 90, 91 , 92, 93, 94, 95, 96, 97, 98, 99, 100, or more CpG loci. Typically, the method detects up to about 10 CpG loci, such as 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10. Typically, the method detects at least 4 CpG loci, such as from about 4 to about 10, such as 4.

As noted above, the CpG loci measured in the method may comprise any one or more loci listed in Table 1 , or associated loci. Typically, at least one of the following loci are measured:

eg 13914893, cg08857201 , cg04207084, cg07858113, cg09706021 , cg19640166, cg21264055, cg01799653, cg05326023, cg02022733, and loci within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides thereof.

More typically, at least one of the following loci are measured: cg13914893, cg08857201 , cg04207084, cg07858113, and loci within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides thereof. Typically, a combination of at least four loci are measured, including at least cg13914893, cg08857201 , cg04207084, and cg07858113 (or loci within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides thereof). In aspects, only four loci are measured, which can be selected from Table 1. However, in such aspects typically cg13914893, cg08857201 , cg04207084, and cg07858113 are measured (or loci within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides thereof).

The method may be used for any type of sample, but typically the sample is a prostate biopsy sample or, more specifically, a needle biopsy sample. In other aspects, the sample is a blood sample, which may contain circulating tumor cells. The sample may also in aspects be a urine sample.

The methods described herein may be followed by methods of treating prostate cancer using any conventional or otherwise known treatment. Once the diagnosis is successfully made, treatment decisions can be made in an informed way that typically leads to better outcomes. The above disclosure generally describes the present invention. A more complete understanding can be obtained by reference to the following specific Examples. These Examples are described solely for purposes of illustration and are not intended to limit the scope of the invention. Changes in form and substitution of equivalents are contemplated as circumstances may suggest or render expedient. Although specific terms have been employed herein, such terms are intended in a descriptive sense and not for purposes of limitation.

Examples

Example 1 - Genomic DNA methylation-derived algorithm enables accurate detection of malignant prostate tissues

ABSTRACT

Introduction: The current methodology involving diagnosis of prostate cancer (PCa) relies on the pathology examination of prostate needle biopsies, a method with high false negative rates partly due to temporospatial, molecular, and morphological heterogeneity of prostate

adenocarcinoma. It is shown herein that molecular markers have a potential to assign diagnosis to a considerable portion of undetected prostate tumors. This study examined the genome-wide DNA methylation changes in PCa in search of genomic markers for the development of a diagnostic algorithm for PCa screening.

Methods: Archival prostate cancer and normal tissues were assessed using genomic DNA methylation arrays. Differentially methylated regions were used for functional assessment, gene-set enrichment and protein interaction analyses, and examination of transcription factor binding patterns. Raw signal intensity data was used for identification of recurrent copy number variations (CNVs). Non-redundant fully differentiating CpGs, which did not overlap CNV segments, were used in an L1 regularized logistic regression model (LASSO) to train a classification algorithm. Validation of this algorithm was performed using a large external cohort of benign and tumor prostate arrays.

Results: Approximately 6,000 probes and 600 genomic regions showed significant DNA methylation changes, primarily involving hypermethylation. Gene-set and protein interaction analyses found an overrepresentation of genes related to cell communications, neurogenesis, and proliferation. Motif enrichment analysis demonstrated enrichment of tumor suppressor binding sites nearby differentially methylated regions. Several of these regions were also found to contain copy number amplifications. Using four non-redundant fully differentiating CpGs, we trained a

classification model with 100% accuracy in discriminating tumors from benign samples. Validation of this algorithm using an external cohort of 234 tumors and 92 benign samples yielded 96% sensitivity and 98% specificity. The model was found to be highly sensitive to detect metastatic lesions in bone, lymph node, and soft tissue, while being specific enough to differentiate the benign hyperplasia of prostate from tumor.

Conclusion: A considerable component of prostate cancer DNA methylation profiles represent driver events potentially established/maintained by disruption of tumor suppressor activity. As few as one CpG from this profile can be used for screening of prostate cancer.

INTRODUCTION

Prostate Cancer (PCa) is the most common malignancy in men, representing the third greatest cause of mortality in the general population after lung and colorectal cancer¹. Current screening protocols for prostate cancer rely on digital rectal examination along with the evaluation of serum levels of prostate-specific antigen (PSA). If a tumor is suspected, trans-rectal, ultrasound- guided, prostate needle biopsies are conducted, followed by a histopathology examination. Major limitations of this approach include a relatively high false negative rate and the requirement for annual follow-ups and repeat sampling, an invasive approach with significant burden on patient healthcare and lifestyle². As such, a significant effort has been made to identify more accurate diagnostic and screening biomarkers for PCa, though to date this effort has been met with limited success in clinical application³.

Among the markers that have gained interest in disease screening is DNA methylation, an epigenetic mechanism that includes modification of the fifth base of cytosine at cytosine-phosphate- guanine (CpG) dinucleotide in the DNA by addition or removal of a methyl group. DNA methylation plays an integral role in the regulation of gene expression and genomic stability, disruption of which can lead to neoplastic transformation, carcinogenesis, and cancer progression⁴. The relative stability of the DNA molecule together with the genome-wide distribution of DNA methylation marks has made it an attractive target for disease biomarker discovery⁵. DNA methylation has proven to possess a great potential in the prediction of many human traits and conditions, including age, post partum depression, childhood stress exposure, tumor class, response to therapy, and cancer progression/metastasis5.

Epigenetic changes have been previously demonstrated in multiple cancers including PCa⁶, with epigenomic signatures of PCa being proposed to be used as both diagnostic and prognostic markers3’⁷. PCa-associated DNA methylation changes have also been found in the urine and

¹ Jemal et al. Cancer J Clin 201 1 ; 61 (2):69-90.

² Wojno et al. J Urol 2015; 193(4): 1 170-7.

³ Gaudreau et al. Biomark Cancer 2016; 8(Suppl 2): 15-33.

⁴ Schenkel et al. Crit Rev Clin Lab Sci 2016; 53(3): 147-65.

⁵ Mikeska et al. Genes 2014; 5(3):821 -64.

⁶ Li et al. J Natl Cancer Inst 2005; 97(2): 103-15.

⁷ Geybels et al. Clin Epigenetics 2016; 8(1 ): 97. serum of patients, raising hopes for non-invasive methods of PCa screenings. These methylation changes have been found in various genes involved in hormonal response, cell-cycle regulation, cell invasion, and DNA damage repair6. In particular, hypermethylation in the promoters of tumor suppressor genes APC, RAR/.3, and GSTP1, has been proposed to be used as a diagnostic marker for PCa⁸. However, these assays have not generated optimal performances, partly because they target selected candidate genes instead of markers discovered in a genome-wide search. The number of studies attempting to produce a diagnostic methylation algorithm for PCa using a genome-wide approach is limited. Furthermore, few studies have conducted a comprehensive genome-wide DNA methylation analysis to reveal the role of DNA methylation in PCa3.

In the present study, we have conducted a genome-wide DNA methylation analysis to describe the DNA methylation changes in PCa. We have investigated potential mechanisms by which differentially methylated genes may be involved in the development of PCa, by examining pathway enrichment and protein interactions. In addition, we have addressed mechanisms that regulate the establishment of differentially methylated regions (DMRs) in PCa by investigating the transcription factor binding patterns nearby the identified segments. Also, we report the copy number variations (CNVs) recurrently happening in PCa and evaluate their associations with the methylation levels of DMRs. Finally, using the most differentiating CpGs, we have generated a classification model to distinguish the tumors from the adjacent benign tissues, and have validated this algorithm using a large independent cohort of benign and tumor prostate samples.

METHODS

Specimen collection

Archival formalin-fixed paraffin-embedded tissues were collected from the Department of Pathology at McMaster University, Ontario, Canada. The slides were reviewed by a pathologist to identify representative tumor tissue blocks. Enrichment of tumor cells was performed by tissue macro-dissection of predetermined areas, as outlined by Haemotoxylin and Eosin staining. Seven- micron thick sections in isolated areas of interest with at least 50% tumor cellularity were dissected to be used as tumor samples. Normal prostate samples were obtained from the adjacent tissues demonstrating no tumor involvement.

Methylation assay and quality assessment

Genomic DNA extraction was conducted using the lllumina FFPE DNA recovery kit.

Following bisulfite conversion, DNA methylation analysis of the samples was performed using the lllumina Infinium methylation 450k bead chip array (San Diego, CA), according to the

manufacturer’s protocol. Both tumor and normal samples were assayed in one experiment to avoid

⁸ Baden et al. J Urol 201 1 ; 186(5):2101-6. batch effect. The resulting methylated and unmethylated signal intensity data were imported into R 3.4.2 for analysis. Normalization was performed using lllumina normalization method with background correction using the minfi package⁹. Probes with detection p-value >0.01 , and those known to contain single nucleotide polymorphisms (SNPs) at the CpG interrogation or single nucleotide extension were removed. All of the samples were examined for genome-wide methylation density, and those deviating from a bimodal distribution were excluded. Factor analysis using multiple dimensional scaling did not reveal any unexplained variation or outliers among the samples. The raw and processed genome-wide methylation microarray data has been deposited to gene expression omnibus (GEO, accession ID: GSE112047).

Identification of a PCa-related methylation profile

DNA methylation analysis was performed using a modification of our previously published protocol^{10 15}. Methylation level for each probe was measured as a beta value, calculated from the ratio of the methylated signals vs. the total sum of unmethylated and methylated signals, ranging between 0 (no methylation) and 1 (full methylation). This value was used for biological interpretation and visualization. For statistical analysis beta values were logit transformed to M-values using the following equation: log2 (beta/1-beta). A linear regression modeling using the limma package¹⁶ was used to identify the differentially methylated probes by testing the association of every CpG site with the level of tumor involvement (0-90%). The generated p-values were moderated using the eBayes function in the limma package and were corrected for multiple testing using Bonferroni method. Probes with a corrected p-value <0.01 and a methylation difference >20% were considered significant. The effect size cut-off (20%) was determined following the examination of the volcano plot of the analysis, as conducted in our previous study¹⁷. The identified probes were examined using an unsupervised hierarchical clustering to ensure their ability in separating the tumors from normal samples.

Gene enrichment analysis and identification of differential methylation interaction hotspots

To identify the gene ontology (GO) terms overrepresented in the genes harboring differentially methylated probes, a gene-set enrichment analysis was performed using the

⁹ Aryee et al. Bioinformatics 2014; 30(10): 1363-1369.

^{1 0} Schenkel et al. J Mol Diagn 2016; 18(6):834-41.

^{1 1} Kerkhof et al. J Mol Diagn 2017; 19(6):905-20.

^{1 2} Kernohan et al. Clin Epigenetics 2016; 8(1 ):91.

^{1 3} Schenkel et al. Clin Epigenetics 2018; 10: 21.

^{1 4} Aref-Eshghi et al. Epigenetics 2017; 12(1 1 ): 923-933.

^{1 5} Schenkel et al. Epigenetics Chromatin 2017; 10(1 ): 10.

^{1 6} Ritchie et al. Nucleic Acids Res 2015; 43(7): e47.

^{1 7} Aref-Eshghi et al. Am J Hum Genet 2018; 102(1 ): 156-174. missMethyl package¹⁸, taking into account the number of CpG sites per gene. GO terms with a Bonferroni corrected p-value <0.01 were considered significant. Only the biological processes were reported. The redundant GO terms were reduced, and following a multiple dimensional scaling, visualized using REViGO tool¹⁹. The relationships across the significant GO terms were plotted in a hierarchical order using GORILLA tool²⁰.

We used EpiMod algorithm²¹ to search for the“interactome hotspots” of differential promoter methylation. In this algorithm, protein expression changes are inferred according to a model of inverse association between the promoter methylation and gene expression. Among the

differentially expressed genes in an interactive network, a hotspot (or epigenetic module [EpiMods]) is a sub-network with an exceptionally large average edge-weight density (combined methylation statistics of the neighboring genes) as compared to the rest of the network21. To assign a statistical significance for the identified hotspots 1 ,000 Monte Carlo randomization of the molecular profiles were conducted as suggested by the algorithm. Interactive network hotspots composed of at least ten genes and FDR <0.01 were reported.

Identification of differentially methylated regions in PCa

To identify genomic regions harboring methylation changes (differentially methylated regions - DMRs), a bump-hunting approach was used by the bumphunter package²². The analysis considered regions with >20% change in the overall methylation between tumor and normal samples with gaps no more than 500 bp among neighboring CpGs. As suggested by the package, 1 ,000 bootstrapping procedures were performed to compute family-wise error rate (FWER). We selected regions containing a minimum of three consecutive probes and FWER <0.01. The identified regions were mapped to CpG islands and coding genes. Gviz package was used for visualization of the DMRs.

Identification of copy number changes using DNA methylation array

To estimate the copy number alterations in the prostate tumor from the Infinium methylation array, the raw methylated and unmethylated intensities from every sample were summed, and quantile normalized using the preprocessCore package²³. The normalized matrix values were divided by the median values of every probe across the normal samples. The divided ratios were

^{1 8} Phipson et al. Bioinformatics 2015; 32(2):286-8.

^{1 9} Supek et al. PloS One 2011 ; 6(7):e21800.

²⁰ Eden et al. Bioinformatics 2009; 10(1 ):48.

²¹ Jiao et al. Bioinformatics 2014; 30(16):2360-2366.

²² Jaffe et al. Int J Epidemiol 2012; 41 (1 ): 200-209.

²³ Bolstad B. preprocessCore: A collection of pre-processing functions. R package version 1.40.0, 2017;

https://github.com/bmbolstad/preprocessCore. then log 10 transformed, smoothed, and segmented using the DNAcopy Bioconductor package²⁴ to identify genomic regions in every sample showing a copy number change. A p-value of <0.01 obtained from 10,000 permutations was used to define a change point during segmentation. The segmented regions with a minimum of five probes and an average log ratio >0.2 or <-0.3

(corresponding to at least one copy amplification/deletion) were selected. Using the

GenomicRanges package²⁵, the segments with a similar pattern of copy number change in both normal and tumor samples were excluded. Segments on chromosome six, overlapping HLA genes, were not considered due to normal variations in their copy numbers. From the remaining segments, those occurring in more than one tumor sample were reported.

Transcription factor binding site enrichment analysis in DMRs

We investigated the enrichment of transcription factor binding motifs in both the identified DMRs and their immediate surroundings (±5kb) using the pipeline recommended by the RTFBSDB package²⁶. First, the entire direct and inferred Homo sapiens transcription factor binding motifs were downloaded from the Cis-BP database²⁷. Every DMR sequence and its ±5kb surroundings were scanned for motif enrichment relative to a background genome of 100,000 base pairs. As recommended by the package, the difference in the GC content of the DMRs and the background genome was accounted for by re-sampling of the background genome to avoid a potential bias due to GC content. The motifs with an enrichment ratio ³1.5 folds and a Bonferroni corrected p-value <0.01 were selected for assessment.

Construction and validation of a DNA methylation-based diagnostic model for PCa

The differentially methylated probes were used to build a classification model to differentiate tumor samples from the normal tissues. Only CpG probes located outside the regions with copy number change were utilized for feature selection. First, a receiver operating characteristic curve analysis (ROC) was performed to identify the most differentiating probes. Those probes with an area under the curve (AUC) of 1.00 were retained. Next, pairwise correlations among the remaining probes were measured to identify and exclude the redundant features with R-squared >0.90. A least absolute shrinkage and selection operator (LASSO) was used to further narrow down the features and train the model, using the glmnet package²⁸. Following 1 ,000 permutations, the shrinkage parameter of lambda with lowest misclassification error was selected and incorporated into the final model. The model was set to generate probability scores ranging 0-1 , representing the

²⁴ Seshan et al. DNA copy number data analysis. 2017; R package version 1.52.0.

²⁵ Lawrence et al. PLoS Comput Biol 2013; 9(8):e10031 18,

²⁶ Wang et al. Bioinformatics 2016; 32(19):3024-6.

²⁷ Weirauch et al. Cell 2014; 158(6): 1431 -43.

²⁸ Friedman et al. J Stat Softw 2010; 33(1 ), 1 -22. chance of a given sample being a tumor. The default binary classifier’s probability threshold of 0.5 was used as classification cut-off. To assess the performance of the model, publically available methylation data from normal and tumor prostate tissues, benign prostate hyperplasia (BPH), and samples of PCa metastasis in other tissues were downloaded from GEO and blindly supplied to the model. Based on the scores and classifications produced by the algorithm for these samples, we measured accuracy, sensitivity, specificity, and AUC as indices of performance for our classifier. The GEO accession IDs and their related publications of the methylation data files used for validation of our algorithm are mentioned here to give credit to the researchers providing these data. Tumor and adjacent benign array files were downloaded from GSE76938²⁹, GSE52955³⁰, GSE47915³¹, GSE5547932, GSE83917³², and GSE38240³³. The normal prostate array data from radical prostatectomy due to bladder cancer, and those with BPH were obtained from GSE55599³⁴. Methylation data of tissues with metastases from prostate were included in the files from

GSE3824033.

Ethics statement

This study has been approved by the Hamilton Integrated Research Ethics Board (#14-700- T). All of the samples and records were de-identified prior to analysis.

RESULTS Study cohort

The study cohort included 31 samples of archival prostate gland tissue with a confirmed diagnosis of prostate adenocarcinoma, assessed by a licensed pathologist. From 16 of these, adjacent normal tissues were collected to be used as the control group. The tumor sections were dissected ensuring a minimum of 50% cancer involvement using macrodissection. There was no overall difference between the age of the subjects in the control group (55.7 ± 7.3) and the tumor group (55.2 ± 9.9).

PCa generates a hypermethylation profile

From a total of 440,532 CpG probes that passed the quality controls, a total of 6, 167 were revealed to have a methylation difference of >20% between the two groups with a multiple testing corrected p-value <0.01 (Table 1 , Figure 1). Out of these CpG sites, only 27 (0.4%) showed a

²⁹ Kirby et al. BMC cancer 2017; 17(1 ):273.

³⁰ Ramalho-Carvalho et al. J Hematol Oncol 2017; 10(1 ):43.

³¹ Naeem et al. BMC Genomics 2014; 15(1 ):51.

³² Fraser et al. Nature 2017; 541 (7637):359-64.

³³ Aryee et al. Sci Transl Med 2017; 5(169): 169ra10.

³⁴ Paziewska et al. Br J Cancer 2014; 1 1 1 (4):781 -9. hypomethylation change. The vast majority of these probes were annotated to a coding gene (n=4,334, 70.2%). A significant number showed an association with regulatory features, including 5,011 (81.2%) being located in or nearby a CpG island, 1 ,959 (31.7%) being annotated to DNase Hypersensitivity Sites and 2,000 (32.3%) located in an enhancer element. Using an unsupervised hierarchical clustering, these probes were shown to be able to completely separate the two groups The degree of hypermethylation was observed to be correlated with the level of tumor cellularity (Figure 2). A correlation analysis between the mean methylation levels of the entire profile and tumor cellularity revealed a Pearson correlation coefficient of 0.92 (Figure 3).

Table 1. CpG loci differentially methylated in prostate cancer.

cg04364728 chrl 845810 0.25 7.198E-21 cg21279510 chrl 8277627 0.29 2.898E-15 cg23207077 chrl 905988 0.20 3.588E-15 cgl9886853 chrl 8277746 0.21 3.337E-14 cg22381068 chrl 906363 0.23 2.246E-15 cg03679305 chrl 9129487 0.28 2.495E-23 cgl6318112 chrl 969254 0.28 4.317E-20 cgl2763828 chrl 9129646 0.23 3.916E-24 cg09248054 chrl 969257 0.31 1.067E-18 cg00310940 chrl 9129648 0.23 1.447E-24 cg04719903 chrl 1181956 0.27 1.566E-17 cgll231958 chrl 9509421 0.22 1.29E-20 cg25594899 chrl 1182226 0.22 2.104 E- 15 cg23251761 chrl 9750061 0.24 2.621E-21 cgl4089984 chrl 1182418 0.25 9.034E-19 cg24859236 chrl 9750213 0.22 1.928E-18 cg06443533 chrl 1182424 0.32 3.523E-18 cgl9858017 chrl 9884719 0.26 3.819E-17 cgll648594 chrl 1566860 0.23 5.27E-15 cg00123104 chrl 9884732 0.27 2.458E-17 cg05700129 chrl 1935125 0.21 2.813E-18 cgl6134717 chrl 11752494 0.23 4.814E-19 cg26067203 chrl 1935289 0.29 4.498E-18 cgl2403889 chrl 11753338 0.21 1.136E-20 cg23621729 chrl 1935445 0.21 5.081E-18 cg03321020 chrl 11958326 0.23 7.907E-19 cg02361803 chrl 2014371 -0.22 8.885E-21 cg03529003 chrl 11994281 0.22 8.329E-22 cgl2526693 chrl 2145258 0.20 1.071E-19 cg00155063 chrl 12227825 0.22 1.145E-17 cgl0397932 chrl 2166155 0.20 1.187E-23 cg08538034 chrl 14928945 0.23 7.704E-21 cgl3488570 chrl 2222253 0.32 7.215E-17 cg00809863 chrl 15251881 0.21 9.161E-22 cg02737619 chrl 2222440 0.22 2.2E-18 cgl0758286 chrl 15481367 0.22 2.919E-19 cg22940848 chrl 2222486 0.24 1.271E-20 cgl8147543 chrl 16276294 0.20 2.23E-20 cgl2053769 chrl 2461413 0.25 2.125E-16 cg07146104 chrl 16489048 0.24 5.534E-19 cg09827752 chrl 2461823 0.37 7.204E-16 cg23072161 chrl 16489115 0.21 1.588E-18 cg01116067 chrl 2461838 0.28 6.515E-17 cg02998240 chrl 16508668 0.22 3.014E-19 cg06839900 chrl 2461900 0.32 1.063E-16 cgl4429204 chrl 16553327 0.22 8.326E-21 cgl5923947 chrl 2461929 0.26 4.829E-21 cg02987928 chrl 16553456 0.20 1.191E-16 cg09808235 chrl 2542588 0.27 1.243E-14 cgl6680438 chrl 16553549 0.22 4.331E-16 cg06775523 chrl 3514921 0.26 5.734E-22 cgl3171718 chrl 16974255 0.20 6.191E-17 cg09187007 chrl 3514990 0.30 7.265E-23 cgl7285883 chrl 17896290 0.22 1.76E-25 cg24953596 chrl 3515194 0.21 2.954E-17 cg00388391 chrl 18459578 0.21 2.744E-20 cg07045089 chrl 3620218 0.22 8.641E-19 cg07536847 chrl 18957232 0.24 4.166E-14 cgl4159342 chrl 3624292 0.24 1.62E-20 cg00794881 chrl 19043573 0.22 6.525E-18 cg02214783 chrl 3688257 0.22 6.502 E- 20 cg26924440 chrl 19276353 0.20 6.414E-20 cgl7175208 chrl 6241179 0.22 3.364E-16 cg27549720 chrl 19992167 0.23 3.392E-16 cgl0976772 chrl 6390595 0.23 1.616E-19 cg24685601 chrl 20512550 0.23 5.247E-19 cg24153044 chrl 6485201 0.22 7.872E-15 cgll651220 chrl 20512944 0.25 4.465E-19 cg27539986 chrl 6664103 0.29 3.005E-24 cg06377106 chrl 20618331 0.24 2.924E-19 cg09159285 chrl 6664134 0.21 8.303 E-22 cg06444282 chrl 20669975 0.24 6.105E-18 cgl9884658 chrl 6664268 0.23 3.12E-20 cg06897478 chrl 20799799 0.24 2.563E-22 cg00808305 chrl 7434171 0.22 8.486E-21 cgl5653910 chrl 20799948 0.22 6.606E-23 cgl8376288 chrl 8181555 0.31 6.323E-22 cg08892236 chrl 21978698 0.23 5.826E-16 cgl0227331 chrl 8181647 0.22 3.974E-20 cg02790379 chrl 22140769 0.23 2.097E-18

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cgl5467646 chrl 22141014 0.29 1.133E-23 cgl8862767 chrl 40137970 0.24 2.113E-21 cg25138553 chrl 22223841 0.21 1.498E-21 cg00990022 chrl 40138052 0.25 1.954E-23 cgl7841765 chrl 22560699 0.26 4.5E-20 cg22851420 chrl 40149650 0.24 5.438E-21 cg09180171 chrl 22677913 0.27 6.722E-18 cgl8438793 chrl 40149837 0.32 4.224E-17 cg26530485 chrl 23496304 0.20 9.767E-22 cg03741406 chrl 40255103 0.21 1.873E-15 cgl4616251 chrl 24648696 0.27 1.446E-22 cg08551248 chrl 40255129 0.20 1.161E-15 cg22176324 chrl 24648851 0.28 4.867E-25 cgl5355146 chrl 40368366 0.23 8.176E-19 cg05036846 chrl 24648984 0.24 2.901E-24 cgl0512203 chrl 40780905 0.21 1.043E-19 cgll709405 chrl 24649398 0.22 3.447E-22 cg20145692 chrl 40781289 0.23 1.042E-14 cgl0706230 chrl 25944514 0.29 1.311E-16 cgl6328007 chrl 41119988 0.21 2.067E-15 cgl6836311 chrl 25944712 0.26 2.44E-16 cgl9689322 chrl 41284639 0.20 1.739E-15 cg05154698 chrl 26202441 0.23 1.091E-14 cgl3150171 chrl 41326892 0.25 8.778E-19 cg20415053 chrl 26527928 0.23 1.671E-14 cgl9619003 chrl 41846758 0.25 3.325E-26 cg04145287 chrl 26552102 0.21 5.965E-19 cg00596048 chrl 41847267 0.29 1.425E-17 cg05770238 chrl 26686587 0.25 4.011E-15 cg06359703 chrl 41847297 0.36 2.548E-16 cg09668030 chrl 27852173 0.26 5.619E-17 cgl9309616 chrl 41851836 0.20 3.302E-19 cgl3920090 chrl 27872303 0.20 7.59E-21 cg27232866 chrl 43251073 0.29 1.749E-15 cg25273602 chrl 29062859 0.20 3.97E-16 cgl9254906 chrl 43251253 0.25 7.696E-17 cg00456651 chrl 31380425 0.21 1.093E-21 cg00778807 chrl 43524347 0.26 1.658E-18 cg07345934 chrl 31845943 0.24 1.19E-15 cg02584756 chrl 43533796 0.25 1.416E-15 cgl8368411 chrl 31845959 0.22 1.313E-14 cg23671221 chrl 44031300 0.22 2.727E-16 cgll573219 chrl 32083031 0.25 4.09E-19 cgl0881128 chrl 44031826 0.23 2.536E-15 cg26833120 chrl 32169568 0.20 2.392E-21 cg20634514 chrl 44703750 0.22 1.621E-21 cg23305408 chrl 32169701 0.24 1.08E-23 cg25363807 chrl 44703923 0.28 4.627E-21 cg05003322 chrl 32169706 0.24 5.437E-25 cgl0431481 chrl 45249875 0.22 2.987E-19 cg00925616 chrl 32410211 0.21 1.386E-17 cg04108939 chrl 45250181 0.28 2.506E-19 cg04881103 chrl 32410413 0.22 3.434E-18 cg04886703 chrl 45250266 0.26 3.196E-20 cgll756095 chrl 32410614 0.27 2.417E-19 cgll448683 chrl 45274099 0.22 2.969E-15 cg05923595 chrl 33547713 0.33 3.404E-26 cg09065413 chrl 45285821 0.22 2.507E-16 cg06851000 chrl 33627109 0.24 3.384E-19 cg27292588 chrl 45285892 0.26 1.591E-16 cg21416692 chrl 33803805 0.21 2.493E-22 cg00329697 chrl 45286062 0.25 4.334E-14 cg22795212 chrl 33938026 0.25 4.391E-14 cg01913970 chrl 45308593 0.22 4.302E-15 cgl4041778 chrl 33938210 0.23 6.733E-15 cgl4796305 chrl 46632581 0.21 4.086E-20 cgl6354201 chrl 33938307 0.31 4.7E-16 cg27636310 chrl 46632696 0.28 1.265E-18 cg24411961 chrl 34642396 0.21 5.776E-15 cgl4709691 chrl 46632871 0.31 1.572E-19 cgl3364230 chrl 35258779 0.21 2.933E-23 cgl9856273 chrl 46668472 0.24 8.212E-22 cgl2126857 chrl 35384669 0.23 1.755E-16 cgl5696662 chrl 46669221 0.25 7.22E-19 cg25035631 chrl 35586358 0.21 1.207E-16 cg24542714 chrl 46669345 0.28 1.774E-23 cgl4615266 chrl 35586649 0.21 1.384E-16 cg25757115 chrl 46913787 0.28 2.339E-18 cgl8131141 chrl 36043002 0.23 6.033E-16 cgl4258341 chrl 46914023 0.38 9.893E-22 cg24685006 chrl 36043014 0.22 2.926E-16 cg00279790 chrl 46914033 0.40 3.326E-22 cg07091016 chrl 36174005 0.31 6.323E-19 cgl3922291 chrl 46914528 0.22 1.649E-21 cg03507534 chrl 36789937 0.24 2.442E-18 cg03257575 chrl 46951318 0.35 6.916E-20 cgl3423759 chrl 37937403 0.23 1.858E-15 cgl9807257 chrl 46951354 0.31 1.101E-16 cg24375409 chrl 38200920 0.40 3.427E-20 cg03401357 chrl 46951477 0.20 3.339E-16 cg04622024 chrl 38201001 0.26 7.586E-22 cg22604316 chrl 46958801 0.21 1.584E-15 cgll664987 chrl 38201123 0.32 2.982E-22 cg06660332 chrl 47009707 0.25 7.417E-19 cg24519393 chrl 38470540 0.26 7.357E-20 cgl4415160 chrl 47010105 0.22 2.037E-17 cg06086731 chrl 38942075 0.20 4.444E-15 cg06760830 chrl 47079672 0.25 3.225E-22 cgl0626816 chrl 39025249 0.33 4.119E-17 cg06087421 chrl 47695138 0.25 3.251E-18 cgll716270 chrl 39025311 0.29 7.603E-17 cg00875272 chrl 47695321 0.21 1.225E-17 cg20286956 chrl 39547918 0.29 2.571E-20 cgl9797376 chrl 47695475 0.24 1.118E-18 cgl3457165 chrl 40105079 0.22 3.311E-22 cg26891410 chrl 47696260 0.21 7.333E-16 cg23037132 chrl 40105664 0.20 2.631E-16 cgl0633601 chrl 47696701 0.20 2.447E-14 cg01656955 chrl 40137966 0.24 2.13E-25 cg25764899 chrl 47697948 0.30 1.429E-17

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cg04363624 chrl 47697965 0.24 1.907E-15 cg05539515 chrl 62784269 0.22 1.456E-21 cg22796507 chrl 47882739 0.24 2.206E-18 cg08845123 chrl 62784332 0.33 5.487E-23 cgll856897 chrl 47998999 0.30 1.313E-14 cg23166865 chrl 63539729 0.27 6.964E-19 cg02486904 chrl 47999051 0.26 1.787E-15 cgl7941572 chrl 63784454 0.24 2.1E-19 cg22524657 chrl 47999163 0.41 2.274E-16 cg02283366 chrl 63785544 0.24 5.891E-21 cg25137711 chrl 48059173 0.23 5.294E-22 cg06962177 chrl 63785946 0.29 4.075E-18 cg09704415 chrl 48937250 0.27 2.267E-19 cgl3906377 chrl 63792695 0.25 1.038E-14 cg01710865 chrl 48937404 0.41 7.932E-21 cg20321153 chrl 63795435 0.21 4.854E-17 cgl8267506 chrl 48937445 0.27 3.149E-22 cg00347677 chrl 63795636 0.27 2.496E-18 cgl6391955 chrl 50881185 0.23 2.774E-18 cg05923687 chrl 63795711 0.27 1.329E-18 cg22711792 chrl 50883329 0.22 7.357E-16 cg21244177 chrl 63795848 0.21 1.376E-18 cg23097402 chrl 50883394 0.21 5.433E-18 cgl0249375 chrl 63795934 0.33 6.015E-17 cgl0512745 chrl 50884480 0.24 5.45E-16 cgl5837212 chrl 63795970 0.20 4.71E-16 cg07362328 chrl 50886393 0.20 3.58E-16 cg21695661 chrl 63796263 0.26 1.571E-23 cg00945234 chrl 50886411 0.21 1.022E-17 cg26262482 chrl 64937345 0.32 2.187E-21 cgl6732616 chrl 50886782 0.26 4.027E-15 cg24306340 chrl 64937451 0.27 1.879E-20 cg25191628 chrl 50886949 0.22 1.436E-21 cg01521258 chrl 64937528 0.24 3.735E-20 cgl2756396 chrl 50886969 0.20 1.272E-22 cg01340542 chrl 65468273 0.22 3.076E-16 cgl7800654 chrl 50888590 0.30 1.423E-17 cgll989330 chrl 65468827 0.25 1.429E-14 cg26560222 chrl 50888826 0.22 6.949E-20 cg08856601 chrl 65730351 0.21 1.162E-16 cgl9380001 chrl 50889427 0.21 1.163E-18 cg09235539 chrl 65730481 0.23 8.006E-18 cgl0776919 chrl 50889442 0.25 1.527E-16 cg09082287 chrl 65730494 0.21 1.821E-17 cg06645033 chrl 50890678 0.24 1.215E-18 cg00466108 chrl 65731689 0.24 1.263E-17 cgll665991 chrl 50893469 0.20 3.652E-16 cg07027116 chrl 65731738 0.25 2.397E-14 cg09941363 chrl 51730449 0.21 1.838E-21 cgl6294013 chrl 66258022 0.24 5.377E-19 cg26251270 chrl 53067832 0.21 2.539E-16 cg22336004 chrl 66258035 0.20 3.436E-17 cg23272399 chrl 53068579 0.24 2.328E-16 cg22488256 chrl 66258046 0.28 1.071E-17 cg02453146 chrl 53068587 0.20 1.937E-15 cg00460049 chrl 66998806 0.28 3.143E-21 cg00397635 chrl 53309162 0.29 1.014E-15 cgl4610403 chrl 66998812 0.31 1.476E-22 cg04918175 chrl 53527424 0.22 9.373E-22 cgl7162576 chrl 66999059 0.29 9.264E-25 cg04765848 chrl 53527576 0.31 5.193E-26 cgl3052034 chrl 66999238 0.31 1.339E-14 cg23092823 chrl 53528612 0.25 1.784E-21 cg00920348 chrl 66999304 0.30 1.625E-17 cg04562138 chrl 53966412 0.21 1.772E-18 cg27558095 chrl 66999588 0.29 8.056E-15 cg09820244 chrl 54790722 0.23 1.466E-21 cg00089915 chrl 66999684 0.23 1.403E-15 cg04605287 chrl 54953486 0.24 1.661E-15 cg02994349 chrl 66999753 0.27 2.25E-16 cg00590761 chrl 55008319 0.28 1.68E-20 cg25203031 chrl 66999813 0.30 2.357E-16 cgl7001034 chrl 55008516 0.21 2.563E-24 cg24110050 chrl 67217853 0.21 4.649E-17 cg21527621 chrl 55013419 0.24 2.829E-24 cgl4207728 chrl 67217886 0.22 1.588E-16 cgl0266490 chrl 55013709 0.27 4.529E-23 cgl7284804 chrl 67218135 0.23 7.863E-20 cgl9302183 chrl 56397400 0.23 1.306E-19 cg25339566 chrl 67218165 0.32 2.707E-21 cg26837800 chrl 56842338 0.22 7.905 E- 24 cgl2940439 chrl 67600707 0.20 2.734E-16 cgll682697 chrl 56992372 0.24 8.63E-25 cg00165323 chrl 70035080 0.26 9.487E-16 cg00848728 chrl 58716018 0.23 5.634E-22 cg00338801 chrl 70035208 0.25 4.659E-17 cg24351410 chrl 58716033 0.26 3.376E-24 cg22812684 chrl 70035392 0.28 3.707E-19 cgll256607 chrl 58716306 0.26 3.892E-24 cg23624008 chrl 70035479 0.28 7.544E-17 cg23723410 chrl 59486037 0.20 4.326E-19 cgl7177995 chrl 70035846 0.23 5.306E-21 cgl5935965 chrl 59550124 0.20 1.215E-20 cg20457732 chrl 71172486 0.28 6.345E-23 cgl9526130 chrl 59612408 0.27 2.564E-16 cg22694818 chrl 75595970 0.21 1.47E-15 cg08625289 chrl 59612492 0.25 3.935E-16 cg08146483 chrl 75602412 0.28 2.469E-18 cg26246897 chrl 59612710 0.25 2.104 E- 15 cg05725004 chrl 76082568 0.22 1.136E-23 cgll425788 chrl 60136100 0.22 1.828E-16 cg20818417 chrl 76082690 0.34 1.557E-18 cg00914726 chrl 60539400 0.21 5.978E-19 cg26940178 chrl 76082888 0.24 2.814E-15 cgl7042098 chrl 61519631 0.23 7.363E-15 cgl2601757 chrl 76540465 0.21 1.194E-18 cg09550810 chrl 61519890 0.20 2.678E-17 cg21526205 chrl 76540574 0.31 6.712E-19 cg23049458 chrl 62660624 0.28 6.255E-19 cg27538686 chrl 76540641 0.26 7.696E-22

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cg25272065 chrl 77334678 0.27 6.248E-23 cgl2647497 chrl 110210265 0.21 4.073E-19 cg02639927 chrl 77334748 0.23 1.564E-17 cg20676696 chrl 110210444 0.28 4.232E-21 cg00347563 chrl 78511600 0.23 1.526E-14 cg02337836 chrl 110210641 0.24 7.377E-20 cg25288420 chrl 78511713 0.22 3.172E-19 cg07219542 chrl 110210770 0.29 1.04E-20 cg04912843 chrl 78511856 0.28 3.788E-17 cg03942855 chrl 110210925 0.40 7.876E-22 cg27315157 chrl 79086197 0.20 3.043E-17 cg25210835 chrl 110254828 0.20 1.998E-14 cgl4319235 chrl 79472282 0.22 4.696E-22 cgl8786873 chrl 110610899 0.22 2.25E-17 cg21113740 chrl 79472343 0.26 1.679E-23 cgll071207 chrl 110611218 0.23 5.424E-20 cg04360793 chrl 79472361 0.34 1.765E-21 cg06215569 chrl 110611465 0.29 2.316E-18 cgl5084543 chrl 79472408 0.30 1.058E-17 cg23660154 chrl 110626540 0.26 2.221E-19 cg26422458 chrl 79472452 0.25 1.434E-20 cg04792863 chrl 110627197 0.21 4.074E-16 cgll654024 chrl 85230119 0.23 1.03E-23 cg24939845 chrl 110627473 0.23 3.956E-14 cg07478468 chrl 85464000 0.30 6.365E-18 cg27432826 chrl 110672769 0.28 2.548E-26 cgl5639684 chrl 85464110 0.30 2.774E-20 cg02103924 chrl 110672857 0.21 1.729E-15 cg06402325 chrl 85464166 0.23 2.234E-19 cg25207248 chrl 110672912 0.22 3.568E-20 cg23106912 chrl 85464261 0.23 1.662E-19 cg01016662 chrl 110673082 0.44 1.036E-25 cgl6683160 chrl 87617710 0.22 1.304E-17 cg09819083 chrl 110673179 0.21 5.951E-19 cg04246763 chrl 87617811 0.29 1.41E-16 cg04043150 chrl 110673319 0.21 1.164E-20 cgl5575982 chrl 87796349 0.20 1.67E-15 cg01791587 chrl 110693985 0.29 5.702E-21 cgl4254720 chrl 90097981 0.24 6.965E-20 cgl3469595 chrl 111813852 0.20 4.843E-21 cgll823511 chrl 91183697 0.25 6.592E-16 cgll574975 chrl 112058304 0.27 5.532E-23 cg20311863 chrl 91184126 0.23 7.472E-15 cg07314829 chrl 112058397 0.20 5.193E-22 cgl2656020 chrl 91185028 0.21 7.447E-15 cgl4669379 chrl 112058559 0.32 4.329E-22 cg22507154 chrl 91185233 0.25 4.246E-21 cg07005055 chrl 113052167 0.31 1.907E-17 cg24884703 chrl 91185422 0.26 3.131E-17 cg07023459 chrl 113265410 0.24 6.264E-22 cgl6058493 chrl 91189167 0.28 2.053E-18 cg21286782 chrl 113265602 0.26 2.138E-22 cgl5469272 chrl 91189314 0.25 8.349E-19 cgl0806711 chrl 113265679 0.20 2.144E-23 cg26568372 chrl 91190173 0.24 4.37E-19 cg22865470 chrl 113286757 0.22 2.001E-17 cgl5452970 chrl 91190620 0.20 4.687E-18 cgl2549600 chrl 113287034 0.23 5.252E-18 cgl4663264 chrl 91192798 0.20 2.901E-16 cgll518509 chrl 114525428 0.26 2.125E-23 cgl2071888 chrl 91195159 0.22 2.03E-16 cg00764109 chrl 114697582 0.24 1.318E-17 cg04560225 chrl 91195336 0.22 9.259E-15 cgl0440578 chrl 115397857 0.21 2.883E-16 cgl6400631 chrl 91300215 0.23 4.382E-16 cg26156256 chrl 116370891 0.26 7.7E-15 cg00644823 chrl 91301461 0.20 6.318E-18 cg24660670 chrl 116371083 0.21 6.294E-17 cg00503383 chrl 91301651 0.32 7.55E-17 cgl5654259 chrl 116371187 0.23 5.044E-15 cgl8235734 chrl 91301731 0.30 2.005E-17 cg24106636 chrl 116381475 0.28 1.355E-15 cgl7799946 chrl 91301962 0.22 1.373E-18 cg21646199 chrl 116381654 0.20 2.312E-14 cgl4179389 chrl 92947961 0.24 5.726E-15 cg27527108 chrl 116711075 0.26 3.111E-16 cg04158367 chrl 92952440 0.26 6.488E-15 cgl7933722 chrl 116711077 0.33 1.63E-17 cg26027669 chrl 92952467 0.24 5.158E-18 cg01824919 chrl 116711339 0.20 5.467E-16 cgl7858328 chrl 92952521 0.24 3.608E-15 cgl6990168 chrl 119526060 0.21 1.425E-15 cgl8060199 chrl 94146495 0.27 2.497E-17 cg02829688 chrl 119527008 0.20 1.7E-16 cgl4995036 chrl 94146705 0.22 1.907E-14 cg21647227 chrl 119527111 0.24 1.14E-20 cgl8344652 chrl 95393096 0.26 1.71E-14 cgl3080379 chrl 119527156 0.20 1.526E-20 cgl6127594 chrl 95393115 0.28 9.212E-15 cg07820868 chrl 119528638 0.22 3.137E-23 cg26227186 chrl 95393138 0.20 3.289E-15 cg02177231 chrl 119529930 0.28 2.695E-17 cg09896412 chrl 98519101 0.24 8.406E-22 cgl0703826 chrl 119532116 0.23 7.293E-19 cgl4991984 chrl 99470129 0.23 7.166E-15 cgl7326555 chrl 119535693 0.23 2.874E-18 cg03120289 chrl 99470550 0.20 2.273E-14 cg24035245 chrl 119535928 0.25 2.201E-22 cg09408571 chrl 101003634 0.21 6.792E-20 cgl7436134 chrl 119536288 0.22 4.727E-16 cg06223162 chrl 101003688 0.20 4.634E-19 cg25386234 chrl 119542159 0.21 2.119E-19 cg00758069 chrl 107682552 0.22 5.655E-15 cgl2659883 chrl 119543057 0.24 1.528E-20 cg09822538 chrl 107682798 0.20 6.936E-15 cg02063759 chrl 119543295 0.26 5.869E-19 cg24346905 chrl 108023249 0.21 5.542E-17 cg03216846 chrl 119543883 0.26 2.607E-17 cg24323958 chrl 108741884 0.21 2.975E-19 cg20247486 chrl 119544329 0.25 1.997E-19

_

cg06764239 chrl 119544772 0.22 3.567E-16 cg23842796 chrl 156358404 0.25 9.698E-15 cg01959730 chrl 119548825 0.32 5.564E-20 cg20433275 chrl 156358408 0.30 7.624E-15 cg09232478 chrl 119548852 0.22 3.303E-18 cg09938227 chrl 156390124 0.26 8.697E-20 cgl0572355 chrl 119549145 0.21 9.679E-17 cg20582655 chrl 156390237 0.23 7.424E-18 cgl3933734 chrl 119550484 0.21 6.824E-16 cg26371731 chrl 156390240 0.30 1.534E-20 cg22230604 chrl 119870287 0.31 6.215E-18 cg23217622 chrl 156405438 0.25 1.669E-17 cg23609985 chrl 119870339 0.28 3.349E-20 cgl5820574 chrl 156406711 0.20 2.346E-18 cg04784699 chrl 119870478 0.27 4.36E-23 cg06355129 chrl 156646293 0.22 1.761E-16 cgl9624849 chrl 145415412 0.30 2.965E-16 cgl8793215 chrl 156674685 0.21 2.962E-21 cgl4036143 chrl 145415441 0.23 3.339E-15 cgl7165580 chrl 156676581 0.24 1.922E-16 cg01000615 chrl 145562817 0.23 2.083E-21 cg02363950 chrl 156676793 0.20 3.916E-21 cg23019889 chrl 146544044 0.23 1.177E-18 cgl2124922 chrl 158150649 0.22 2.328E-16 cgl0124710 chrl 146544267 0.28 4.468E-19 cg25683325 chrl 158151058 0.23 1.552E-16 cgl6237891 chrl 146544645 0.26 1.715E-18 cgl5549973 chrl 159823687 0.20 3.359E-20 cg03526459 chrl 146549940 0.25 3.696E-18 cgl0400707 chrl 160369840 0.21 5.295E-19 cg02487331 chrl 146550467 0.21 4.756E-17 cgl4710465 chrl 160369869 0.21 3.495E-21 cg20449590 chrl 146551201 0.38 7.232E-20 cg24367957 chrl 161931993 0.23 1.806E-21 cg06871074 chrl 146551565 0.21 1.204E-19 cg04510153 chrl 162660951 0.23 3.144E-24 cg21908235 chrl 146551744 0.31 1.498E-22 cgl7133668 chrl 162792177 0.22 4.479E-15 cgl6700924 chrl 146552102 0.24 2.875E-18 cg05341781 chrl 164723567 0.22 6.76E-23 cg00044796 chrl 146552390 0.24 1.667E-17 cg07135032 chrl 165322099 0.23 1.219E-18 cgl6409339 chrl 146556239 0.23 2.53E-15 cg22629111 chrl 166135208 0.20 4.354E-19 cgl6277128 chrl 146556479 0.30 1.386E-16 cg04138112 chrl 167090618 0.28 5.38E-18 cg00693978 chrl 146556675 0.20 1.154E-18 cgl3958426 chrl 169396637 0.33 8.876E-21 cg25200152 chrl 147790458 0.26 3.341E-20 cg00002719 chrl 169396706 0.43 4.396E-21 cgl3502125 chrl 147826191 0.21 6.779E-17 cg08104202 chrl 169396712 0.39 2.566E-22 cgl5067806 chrl 149146748 0.24 3.189E-14 cg23818870 chrl 169396785 0.31 1.319E-23 cg20300343 chrl 149719461 0.27 1.04E-17 cgl6998150 chrl 169396834 0.30 3.13E-22 cg01705587 chrl 149889364 0.22 1.375E-21 cg08047907 chrl 169396858 0.36 6.587E-21 cg20785674 chrl 150123490 0.23 2.357E-20 cg24808280 chrl 169396868 0.34 1.483E-20 cg26574003 chrl 150186289 0.27 7.678E-17 cgl4826711 chrl 169396909 0.27 9.681E-21 cg03763518 chrl 150245044 0.20 1.986E-20 cgl6136262 chrl 169429604 0.28 1.315E-25 cg07119434 chrl 151103642 0.24 3.122E-19 cg25464921 chrl 169429698 0.31 4.157E-26 cg26331172 chrl 151118299 0.29 4.645E-23 cg23089825 chrl 170630558 0.20 2.528E-15 cgl3331550 chrl 151118416 0.28 1.071E-19 cg07149609 chrl 170630734 0.24 1.321E-17 cg25199322 chrl 151693838 0.25 1.679E-20 cg06267617 chrl 172291727 0.20 2.575E-20 cgll690979 chrl 151694320 0.25 1.105E-22 cg09183124 chrl 173092323 0.27 5.112E-25 cgl0959711 chrl 153509096 0.21 2.565E-24 cgl6517394 chrl 173176362 0.23 8.936E-23 cg23499956 chrl 153584920 0.22 5.948E-21 cg26315984 chrl 173176501 0.22 7.211E-21 cgl3740187 chrl 154164699 0.20 3.437E-20 cg06372962 chrl 173638690 0.21 4.364E-18 cgl0445911 chrl 154971922 0.24 2.946E-14 cgl5883716 chrl 173638701 0.23 8.113E-18 cgl5627710 chrl 154972140 0.23 2.454E-17 cg02958263 chrl 174769548 0.27 2.95E-21 cg05778494 chrl 155165346 0.20 1.58E-17 cgl7516247 chrl 174933574 0.21 8.097E-22 cg08170787 chrl 155290535 0.21 1.48E-17 cg22081371 chrl 177827903 0.22 4.201E-15 cg08574629 chrl 155290542 0.22 2.603E-18 cg26004771 chrl 178456093 0.23 3.483E-16 cg22877509 chrl 155290607 0.24 5.463E-21 cg08186924 chrl 179544721 0.26 1.874E-21 cgl9516515 chrl 155290614 0.22 2.063E-21 cgl3931925 chrl 179545216 0.28 4.723E-20 cg24006126 chrl 155290813 0.23 7.803E-17 cgl9016332 chrl 179545294 0.24 1.079E-20 cgl2065285 chrl 155946346 0.26 1.515E-22 cg09671258 chrl 180202530 0.26 2.392E-16 cgl8276016 chrl 156076340 0.28 1.727E-18 cgl8063017 chrl 180204974 0.21 1.065E-20 cg24674445 chrl 156076363 0.27 7.23E-16 cgl2604950 chrl 180882287 0.21 2.938E-18 cg23274561 chrl 156084271 0.21 1.593E-24 cg02156380 chrl 180882591 0.27 3.78E-25 cg08881019 chrl 156096178 0.22 7.208E-24 cg06692785 chrl 180882681 0.27 7.657E-25 cg21996227 chrl 156130826 0.20 8.008E-19 cg04276005 chrl 180895868 0.25 1.334E-22 cgl2062819 chrl 156358231 0.28 1.029E-14 cgl9866866 chrl 182026044 0.26 2.249E-21 Meth.

probe ID Chr. Position P-value probe ID Chr. Position P-value

Diff. _ Diff.

cg03982831 chrl 182669315 0.22 7.088E-20 cg00901051 chrl 208132490 0.27 2.207E-16 cg02710296 chrl 182921851 0.24 1.727E-14 cgl0236452 chrl 208132590 0.27 7.808E-15 cg25837803 chrl 186649909 0.27 2.27E-15 cg07097417 chrl 212002770 0.22 4.583E-23 cgl6101346 chrl 186650479 0.22 6.533E-16 cg07569918 chrl 212002970 0.23 1.178E-20 cgl2725760 chrl 192873912 0.24 7.646E-21 cg24511404 chrl 212607111 0.23 2.885E-24 cg06371502 chrl 197879766 0.26 3.484E-17 cgl5130102 chrl 213090116 0.22 2.657E-21 cg25212090 chrl 197882170 0.21 3.436E-18 cg04607844 chrl 213090203 0.26 5.166E-21 cgl5544654 chrl 197882295 0.24 5.957E-16 cgl2596505 chrl 213090240 0.21 2.598E-22 cgl6353006 chrl 197882469 0.26 5.195E-18 cg26926612 chrl 214153294 0.23 1.209E-15 cg08883223 chrl 197888880 0.24 7.791E-16 cg07029873 chrl 217311014 0.25 9.008E-19 cgl5198094 chrl 200003342 0.23 1.264E-22 cg06634716 chrl 217311151 0.24 2.481E-20 cgl0513702 chrl 200003800 0.29 4.271E-26 cg21784383 chrl 217311172 0.27 3.477E-20 cg23258678 chrl 200004095 0.34 4.467E-23 cg00913949 chrl 217311511 0.23 2.206E-16 cgl5062377 chrl 200004205 0.29 2.949E-27 cg25755575 chrl 217311531 0.24 9.029E-18 cgl6046444 chrl 200004265 0.22 1.201E-15 cg22118524 chrl 217311547 0.20 2.642E-16 cgl6103959 chrl 200004529 0.26 8.741E-23 cgl7164063 chrl 218330093 0.24 1.238E-17 cg01941755 chrl 200004582 0.22 2.057E-19 cgl0484211 chrl 218547935 0.20 4.351E-20 cg02779944 chrl 200004584 0.25 2.855E-21 cg03224396 chrl 221017300 0.22 1.613E-18 cgl5130541 chrl 200004637 0.21 1.82E-20 cg03536711 chrl 221509067 0.22 1.484E-19 cgl2730323 chrl 200004757 0.24 6.617E-21 cg08892600 chrl 223538601 0.23 6.967E-21 cg07208853 chrl 200005219 0.26 5.125E-21 cgl0502231 chrl 224363449 0.26 3.833E-20 cg24553673 chrl 200005453 0.21 2.681E-17 cgl7239057 chrl 224363575 0.25 2.68E-22 cg07926895 chrl 200005833 0.21 2.922E-21 cg22444124 chrl 226867960 0.27 1.874E-18 cgl0972873 chrl 200007592 0.28 1.075E-25 cgl4789818 chrl 227748712 0.25 2.948E-20 cgl6993043 chrl 200008026 0.32 2.588E-18 cg20699586 chrl 227748719 0.27 2.651E-19 cg04097639 chrl 200009830 0.27 2.87E-16 cgl0962762 chrl 228075749 0.20 1.257E-14 cg03257172 chrl 200010283 0.26 2.808E-17 cg09316122 chrl 228195522 0.21 2.368E-14 cg04025964 chrl 200010788 0.30 3.556E-18 cg24848599 chrl 228604800 0.21 3.381E-18 cg02773945 chrl 200011858 0.22 1.42E-15 cg25874119 chrl 228633904 0.24 6.975E-22 cg22810423 chrl 200272180 0.20 8.154E-19 cg00655913 chrl 228633920 0.31 3.192E-21 cgl3300273 chrl 200842890 0.30 6.811E-19 cg25622154 chrl 228657536 0.22 1.099E-17 cg21422700 chrl 201229247 0.28 4.238E-25 cg06585233 chrl 229543009 0.21 1.29E-17 cg04223671 chrl 201509316 0.41 1.883E-22 cg03940848 chrl 229543112 0.28 1.111E-17 cg04121938 chrl 201509415 0.22 5.033E-25 cg08855395 chrl 231296818 0.23 5.131E-20 cgl0574566 chrl 203377808 0.23 3.93E-25 cglll92416 chrl 231296968 0.21 3.998E-17 cg27173151 chrl 203598330 0.21 1.043E-17 cgl4009098 chrl 234041306 0.25 1.94E-18 cg26253438 chrl 203598623 0.23 2.069E-14 cgl3420364 chrl 234857659 0.23 5.34E-22 cg02457623 chrl 203599089 0.26 9.207E-19 cgl8792146 chrl 235105751 0.25 1.005E-18 cg07026666 chrl 204050380 0.20 5.176E-21 cg24716879 chrl 235105872 0.25 2.348E-20 cgl2638737 chrl 204120607 0.25 2.228E-20 cg00040837 chrl 236081097 0.21 1.259E-18 cg02990368 chrl 204120649 0.25 3.266E-23 cgl8879590 chrl 236306640 0.22 4.43E-16 cg27549944 chrl 204328843 0.21 1.969E-22 cgl5031661 chrl 240256603 0.24 3.561E-17 cg09085216 chrl 204329081 0.23 4.355E-22 cgl8181201 chrl 242686709 0.20 1.348E-15 cg04705659 chrl 204329107 0.21 1.862E-20 cgl6126286 chrl 243646235 0.24 3.237E-16 cg24864241 chrl 204329158 0.27 2.501E-23 cg00705059 chrl 244080368 0.21 8.839E-15 cg21581873 chrl 204329307 0.20 1.626E-22 cg20678442 chrl 244893503 0.35 8.886E-19 cg08159989 chrl 205326071 0.24 1.837E-14 cgl5176829 chrl 246952215 0.25 1.021E-22 cg07429623 chrl 205326201 0.24 1.326E-21 cg03596016 chrl 246952362 0.42 5.194E-21 cg03585778 chrl 205537837 0.26 1.206E-15 cg08535928 chrl 246952495 0.27 5.798E-21 cgl8328206 chrl 206681378 0.24 1.34E-16 cg03340119 chrl 246952508 0.26 3.67E-23 cg22356428 chrl 206687071 0.21 7.18E-22 cg26276327 chrl 247511469 0.23 4.379E-19 cg03990033 chrl 208084030 0.21 2.171E-18 cg25065716 chrlO 1422865 0.20 5.17E-18 cgl6291276 chrl 208084071 0.24 6.046E-19 cgl7861863 chrlO 1454387 0.31 1.11E-16 cgl9591881 chrl 208084640 0.22 1.733E-18 cgl4824052 chrlO 2951326 0.20 4.953E-19 cgl3298199 chrl 208132388 0.27 4.476E-19 cg06188744 chrlO 3108651 0.26 2.917E-19

cg23782734 chrlO 3109041 0.28 3.988E-24 cgl0198294 chrlO 28616726 0.22 7.929E-22 cg07198194 chrlO 3109053 0.33 3.46E-20 cg06197966 chrlO 29948324 0.22 1.797E-19 cg03917666 chrlO 3977608 0.22 6.5E-26 cg27268352 chrlO 30387860 0.24 5.647E-22 cgl2506775 chrlO 5734571 0.26 1.03E-23 cg02059509 chrlO 30405144 0.21 9.468E-21 cg01476568 chrlO 5734716 0.28 3.882E-20 cg26579601 chrlO 30724020 0.26 1.619E-21 cgl0119075 chrlO 7709738 0.33 3.593E-25 cgl9596273 chrlO 30724086 0.24 2.548E-22 cg09445472 chrlO 7709962 0.26 4.823E-19 cgl4847502 chrlO 30724194 0.21 2.252E-23 cgl0008757 chrlO 8097183 0.21 7.379E-16 cg25680628 chrlO 30724274 0.29 6.647E-24 cgl4327531 chrlO 8097331 0.26 6.869E-18 cg26647332 chrlO 31073467 0.29 7.914E-17 cgl3409449 chrlO 8097354 0.31 7.484E-17 cgll944757 chrlO 31422942 0.22 2.029E-15 cgl5267232 chrlO 8097689 0.33 1.165E-23 cglll47278 chrlO 34062234 0.21 2.309E-14 cg04249706 chrlO 11206772 0.29 8.251E-18 cgl3853894 chrlO 34393934 0.23 2.903E-23 cg25761326 chrlO 11206792 0.23 3.575E-19 cg03171770 chrlO 43393728 0.23 3.263E-18 cgll482422 chrlO 11206813 0.22 1.845E-18 cgll986813 chrlO 43429144 0.42 4.423E-19 cgl7775621 chrlO 11206838 0.21 4.059E-18 cgl7053251 chrlO 43429459 0.31 1.932E-19 cg26150462 chrlO 11206868 0.25 5.134E-21 cg07825347 chrlO 43600497 0.24 3.17E-20 cgl2178980 chrlO 11206870 0.30 1.125E-20 cg07638650 chrlO 43697849 0.28 1.806E-24 cg22738219 chrlO 13043313 0.28 8.804E-15 cg23136139 chrlO 43697918 0.24 1.683E-22 cg22750254 chrlO 13043421 0.20 1.181E-14 cg02636041 chrlO 43698008 0.45 4.309E-22 cg25032745 chrlO 15481695 0.22 1.613E-20 cgl2451631 chrlO 43698141 0.55 1.511E-19 cg27177554 chrlO 16562102 0.28 1.101E-18 cg01083633 chrlO 44162781 0.22 2.691E-18 cg02236650 chrlO 17269775 0.22 7.103E-19 cg25888561 chrlO 44163067 0.40 1.452E-19 cg20198108 chrlO 17270091 0.20 1.093E-14 cg27608999 chrlO 45914276 0.32 8.638E-28 cg06460869 chrlO 17270094 0.25 3.787E-14 cg04194494 chrlO 45914450 0.36 1.197E-27 cg05151811 chrlO 17270250 0.21 6.766E-16 cg21981270 chrlO 45914525 0.39 1.115E-26 cg08918274 chrlO 17270300 0.23 6.815E-18 cgl6831085 chrlO 45914645 0.35 4.915E-21 cgl5115171 chrlO 17604829 0.22 1.687E-18 cgl0069493 chrlO 45914688 0.26 2.38E-24 cg26803268 chrlO 18549536 0.28 1.162E-22 cg00675569 chrlO 45914840 0.33 3.779E-22 cgl8959207 chrlO 18549686 0.21 9.919E-24 cg09806262 chrlO 45914949 0.25 1.067E-24 cg02635932 chrlO 18549778 0.26 6.753E-22 cg07355189 chrlO 45923374 0.24 5.652E-16 cgl9998294 chrlO 18629497 0.22 4.259E-19 cg09197112 chrlO 46992448 0.25 4.915E-23 cg05719612 chrlO 18629545 0.22 2.373E-19 cg07041470 chrlO 46993210 0.25 9.209E-24 cg03103919 chrlO 18629674 0.20 2.307E-16 cgl3722700 chrlO 46993502 0.24 3.799E-17 cgl5169374 chrlO 18629677 0.21 2.566E-17 cg04425920 chrlO 50604518 0.27 1.656E-18 cgl2733607 chrlO 21813501 0.29 1.153E-26 cgl2052765 chrlO 50816963 0.22 6.58E-17 cg03891590 chrlO 21814313 0.23 2.49E-25 cgl4156751 chrlO 50976571 0.21 4.768E-19 cg26492368 chrlO 22634733 0.23 9.363E-16 cg05184377 chrlO 50976646 0.22 8.022E-17 cg07355157 chrlO 23385780 0.20 2.807E-22 cg08739651 chrlO 51784888 0.23 7.817E-22 cg09403666 chrlO 23461493 0.22 5.03E-16 cg23194719 chrlO 52177823 0.27 1.979E-21 cgl4568830 chrlO 23463243 0.22 5.037E-18 cg25575732 chrlO 52177880 0.21 1.784E-21 cg06550984 chrlO 23480002 0.20 8.993E-20 cg05977109 chrlO 52178181 0.25 3.851E-22 cgl6366546 chrlO 24672795 0.20 8.042E-19 cg09425247 chrlO 52178225 0.29 1.093E-21 cg26249873 chrlO 25465430 0.20 4.181E-24 cgl0298052 chrlO 57391055 0.21 5.769E-16 cg08441170 chrlO 26223100 0.21 2.667E-15 cg09696939 chrlO 60272079 0.39 7.326E-23 cg23771603 chrlO 26223310 0.21 5.2E-15 cg01316378 chrlO 63629580 0.20 2.459E-14 cg09084462 chrlO 27220234 0.24 6.419E-22 cg06767766 chrlO 70321383 0.23 2.315E-16 cgl4776321 chrlO 27220441 0.24 5.277E-21 cg23350336 chrlO 70321554 0.33 2.122E-21 cg02161900 chrlO 28035631 0.21 1.93E-20 cgl2630147 chrlO 70321574 0.34 9.073E-23 cg02249292 chrlO 28035655 0.21 1.203E-19 cg02774862 chrlO 70321580 0.36 2.478E-24 cgl7918002 chrlO 28035719 0.22 3.951E-23 cg20326704 chrlO 70321770 0.23 9.575E-18 cg08815081 chrlO 28035731 0.22 2.765E-24 cg02378006 chrlO 73026288 0.21 4.835E-19 cg27303223 chrlO 28035822 0.21 3.713E-17 cg24331301 chrlO 73156377 0.32 6.352E-26 cg05485137 chrlO 28035864 0.24 1.418E-20 cgl5323528 chrlO 73156427 0.30 1.246E-25 cg07964848 chrlO 28035894 0.25 1.846E-19 cgl5763670 chrlO 73473235 0.25 2.031E-24 cgl4947429 chrlO 28036151 0.27 1.141E-20 cgl9407453 chrlO 73473423 0.20 7.192E-24

cg21105787 chrlO 73847257 0.24 1.132E-24 cg27165884 chrlO 99473085 0.21 2.094E-16 cg01498231 chrlO 73847259 0.20 4.902E-23 cg06679087 chrlO 99473206 0.33 2.737E-15 cgl3997668 chrlO 73847532 0.25 8.378E-16 cg06616710 chrlO 99473224 0.25 1.024E-17 cg09661010 chrlO 73848153 0.23 8.422E-16 cg24500959 chrlO 99474813 0.22 6.341E-15 cgl0983208 chrlO 73848320 0.21 1.269E-19 cg22831607 chrlO 99531797 0.27 1.047E-16 cg26435178 chrlO 73848458 0.21 4.698E-19 cg07834955 chrlO 99531879 0.32 2.748E-20 cg07904073 chrlO 74017122 0.25 1.996E-20 cg04991805 chrlO 99790910 0.24 3.352E-15 cgl2799885 chrlO 74020976 0.33 3.007E-17 cgl6674860 chrlO 100206094 0.24 1.911E-15 cg25104124 chrlO 74021022 0.24 5.384E-17 cgl8499443 chrlO 100993553 0.20 1.378E-19 cgl6716883 chrlO 74079772 0.22 4.439E-17 cg08927006 chrlO 100993556 0.22 2.076E-18 cgl7723653 chrlO 75407823 0.30 6.495E-23 cgl3737332 chrlO 100993583 0.22 6.685E-18 cgl2317414 chrlO 75407991 0.32 4.088E-23 cgl7863743 chrlO 100993587 0.26 1.339E-18 cgl9714985 chrlO 77043608 0.29 1.906E-25 cg09511126 chrlO 100993597 0.21 1.496E-20 cg23024158 chrlO 78011952 0.21 1.299E-21 cgl0441934 chrlO 100995640 0.23 9.286E-21 cgl9008877 chrlO 78157854 0.22 9.48E-24 cg03388193 chrlO 100996070 0.23 1.966E-20 cgl6055185 chrlO 79150517 0.21 1.502E-22 cg22891862 chrlO 101279697 0.24 2.46E-19 cg01858517 chrlO 79396584 0.25 9.686E-17 cg23536629 chrlO 101279944 0.35 6.914E-22 cg27586487 chrlO 79687289 0.22 1.975E-19 cgl5338327 chrlO 101280209 0.33 5.296E-24 cgl6680677 chrlO 80008481 0.24 6.284E-20 cg24331598 chrlO 101280256 0.32 1.162E-22 cg22609785 chrlO 80416672 0.20 1.855E-20 cg01177167 chrlO 101280523 0.32 9.123E-21 cg25034155 chrlO 80945359 0.23 1.582E-20 cg26075184 chrlO 101281703 0.22 3.309E-16 cg20744163 chrlO 80999841 0.25 9.378E-20 cg02792168 chrlO 101281924 0.20 8.276E-17 cg26654807 chrlO 81002218 0.22 1.354E-14 cg01987516 chrlO 101282726 0.24 4.104E-19 cgl7853216 chrlO 81002480 0.26 9.276E-15 cg23904955 chrlO 101282759 0.21 5.93E-19 cg02283485 chrlO 81003020 0.21 4.132E-16 cgll081894 chrlO 101283847 0.22 1.817E-21 cg20543544 chrlO 81003657 0.21 7.027E-17 cgl9103219 chrlO 101287059 0.21 4.857E-19 cg22653140 chrlO 81214225 0.26 1.716E-21 cg03036592 chrlO 101287839 0.20 6.579E-19 cg09614479 chrlO 81967536 0.20 8.429E-16 cg04972745 chrlO 101287846 0.26 3.66E-18 cgl9423196 chrlO 82049429 0.22 1.069E-18 cg02798576 chrlO 101290168 0.27 8.814E-21 cg05869699 chrlO 82258734 0.24 9.912E-21 cgl0377903 chrlO 101290699 0.28 1.043E-16 cgl7655415 chrlO 89802559 0.21 4.262E-18 cg04190875 chrlO 101291092 0.23 6.318E-20 cg24035164 chrlO 93646991 0.27 6.131E-20 cg03711485 chrlO 101296036 0.24 1.261E-17 cg04192867 chrlO 93647053 0.25 2.119E-17 cg04669815 chrlO 101296619 0.31 1.747E-20 cgll750133 chrlO 93647217 0.22 1.494E-14 cg24376776 chrlO 101297245 0.33 3.192E-23 cgl5732502 chrlO 93647300 0.31 2.346E-16 cg23615741 chrlO 101297642 0.32 3.687E-18 cgl9116429 chrlO 93647563 0.23 4.124E-16 cgl8267049 chrlO 101875028 0.24 1.828E-20 cgl8484034 chrlO 93647648 0.24 3.43E-19 cg03679755 chrlO 101875035 0.24 7.083E-19 cg22579265 chrlO 94180383 0.32 2.764E-20 cg00557947 chrlO 102419245 0.22 1.456E-16 cg01297808 chrlO 94180551 0.29 4.035E-22 cg00272971 chrlO 102419564 0.23 2.393E-18 cgl9305681 chrlO 94821657 0.26 7.309E-18 cg03943218 chrlO 102419600 0.21 1.189E-15 cg00790395 chrlO 94822172 0.28 2.813E-16 cg07099331 chrlO 102419617 0.26 9.578E-18 cg05127821 chrlO 94822908 0.34 3.567E-22 cg26540559 chrlO 102447443 0.25 2.314E-16 cg22044002 chrlO 94825547 0.23 1.954E-17 cg20100910 chrlO 102475429 0.23 1.633E-20 cg00714725 chrlO 94825576 0.32 6.62E-17 cg22964842 chrlO 102495141 0.32 1.72E-20 cgl4375937 chrlO 94825667 0.21 1.853E-14 cg26596964 chrlO 102495354 0.33 1.357E-20 cgl7011709 chrlO 94826053 0.21 1.643E-16 cg24686074 chrlO 102497666 0.23 2.933E-14 cg06857304 chrlO 94826314 0.22 4.448E-18 cg08823110 chrlO 102589840 0.22 3.465E-18 cg02466572 chrlO 94826319 0.29 5.148E-21 cgll697427 chrlO 102590168 0.24 6.703E-20 cgl0556384 chrlO 94828103 0.20 3.061E-14 cg24146331 chrlO 102590225 0.20 6.194E-21 cgl8082515 chrlO 95197126 0.21 4.624E-23 cg27454883 chrlO 102626432 0.22 3.061E-17 cg06154313 chrlO 95360494 0.20 1.206E-16 cg26582768 chrlO 102792043 0.23 3.274E-16 cg06833709 chrlO 95517498 0.21 3.04E-17 cg06154084 chrlO 102792249 0.28 3.496E-16 cg07793207 chrlO 95517529 0.26 2.602E-21 cgl6448058 chrlO 102880841 0.22 3.119E-15

_

cgl8727742 chrll 288301 0.22 5.417E-16 cg07189401 chrll 19736333 0.22 3.161E-17 cg06632214 chrll 314074 0.32 6.266E-21 cg04290346 chrll 20177852 0.21 2.177E-15 cgl4468692 chrll 504784 0.20 3.479E-15 cgl3445796 chrll 20181725 0.21 1.507E-15 cg23927970 chrll 504933 0.23 9.507E-15 cg02878244 chrll 20181911 0.22 1.419E-14 cg23687466 chrll 504937 0.27 4.152E-14 cg23632985 chrll 20184637 0.24 1.953E-16 cg00249511 chrll 627152 0.25 5.783E-17 cg26142412 chrll 20185077 0.22 1.033E-19 cg25774643 chrll 627175 0.22 1.059E-15 cg27142536 chrll 20618198 0.29 1.673E-21 cg02659920 chrll 726335 0.20 4.084E-15 cg02027945 chrll 20618230 0.39 6.128E-18 cg06085985 chrll 830527 0.22 4.335E-15 cgl9859290 chrll 20618399 0.33 7.313E-20 cgl3104938 chrll 843956 0.24 1.2E-19 cg27603915 chrll 20692113 0.22 8.11E-19 cg01097384 chrll 1358675 0.22 8.871E-18 cg07777008 chrll 27015808 0.29 2.662E-22 cg25590114 chrll 1661201 -0.22 9.237E-18 cgl5621260 chrll 27015813 0.35 7.24E-21 cg08269485 chrll 1769382 0.23 2.843E-16 cg04622802 chrll 27015872 0.26 8.322E-19 cg07592963 chrll 2890649 0.21 3.263E-14 cg01649773 chrll 27015991 0.21 3.337E-19 cg03143849 chrll 2904951 0.23 3.007E-21 cgl2164612 chrll 30037833 0.21 1.04E-17 cgl7265994 chrll 2905024 0.28 1.919E-22 cgll972677 chrll 30605704 0.25 1.165E-14 cg21799346 chrll 2905372 0.31 1.978E-15 cg24332783 chrll 31818791 0.24 4.875E-15 cgl4488317 chrll 3181446 0.29 7.394E-26 cgl8988498 chrll 31824262 0.22 8.158E-16 cgl3634736 chrll 3181575 0.25 2.369E-23 cg20014398 chrll 31825792 0.24 8.518E-17 cg22074576 chrll 3181726 0.36 7.062E-22 cg09537620 chrll 31826574 0.29 8.141E-18 cgll678461 chrll 3181822 0.26 3.001E-24 cgl8372607 chrll 31827084 0.27 5.793E-21 cg23357130 chrll 3181928 0.45 1.384E-22 cg05490712 chrll 31838674 0.22 1.611E-16 cgl3782615 chrll 4079556 0.27 3.668E-25 cg09656389 chrll 31839790 0.23 8.039E-18 cg26730416 chrll 4233502 0.27 3.658E-16 cg07329360 chrll 31841768 0.23 3.994E-19 cg26678920 chrll 6341888 0.22 2.655E-14 cgll741189 chrll 31843886 0.21 5.271E-20 cgl0064871 chrll 6341908 0.20 3.148E-18 cg03405909 chrll 31845639 0.28 8.01E-23 cg26120958 chrll 6439806 0.25 1.766E-22 cg03692563 chrll 31846414 0.23 3.25E-19 cg03559682 chrll 6439864 0.25 1.806E-19 cg08364561 chrll 31846844 0.30 6.407E-20 cg06176750 chrll 7112356 -0.23 1.767E-21 cg07441518 chrll 31846849 0.22 7.864E-19 cg24575083 chrll 7695485 0.21 3.073E-14 cgl2500879 chrll 31848649 0.20 1.255E-14 cgl6281276 chrll 7695528 0.22 5.145 E- 14 cg20019985 chrll 32008961 0.24 3.671E-15 cg20039048 chrll 8305302 0.25 7.452E-25 cg25247290 chrll 32461212 0.26 9.406E-16 cg08726522 chrll 8739587 0.30 3.918E-26 cgl2691382 chrll 33037792 0.23 2.364E-15 cgl9237879 chrll 9113458 0.22 9.433E-16 cg26268276 chrll 33038313 0.23 4.156E-18 cg06126019 chrll 9253566 0.21 3.206E-21 cg06560887 chrll 33890371 0.25 1.044E-16 cgll624479 chrll 9285586 0.22 9.952E-19 cg09089242 chrll 33892236 0.23 2.96E-21 cg23204908 chrll 9824185 0.23 3.599E-21 cg06148118 chrll 33892246 0.23 6.228E-23 cgl6931664 chrll 11169707 0.20 4.141E-17 cg07541559 chrll 34288225 0.22 3.516E-23 cg24543696 chrll 12031046 0.24 4.698E-18 cgl8437209 chrll 35105199 0.24 9.125E-22 cg23352146 chrll 12701929 0.25 6.892E-16 cg20143092 chrll 35160330 0.26 1.812E-15 cgl4381919 chrll 12701969 0.22 1.422E-15 cgl5536165 chrll 35639492 0.22 1.749E-16 cg08148891 chrll 13030309 0.24 1.533E-20 cg08714753 chrll 35639590 0.23 2.034E-16 cg20098471 chrll 13032613 0.28 3.762E-16 cg04573276 chrll 35639632 0.30 1.757E-15 cgl5603424 chrll 13300592 0.24 6.675E-15 cg23083315 chrll 35639656 0.27 4.316E-18 cg05950572 chrll 14004854 0.22 2.973E-16 cg26451547 chrll 36397596 0.24 4.25E-25 cg24304093 chrll 14926738 0.32 5.302E-19 cg08124446 chrll 43596529 0.25 1.117E-16 cgl4768245 chrll 14926780 0.24 8.108E-20 cg01681847 chrll 43605269 0.21 1.205E-15 cg06535308 chrll 17497693 0.22 6.77E-21 cg04970352 chrll 44327399 0.27 7.927E-21 cg05183931 chrll 17717588 0.25 6.785E-16 cg07393734 chrll 44341451 0.21 4.084E-15 cg05756029 chrll 18230754 0.21 1.842E-17 cg01889574 chrll 44590889 0.23 2.173E-19 cgll095319 chrll 19263864 0.24 2.023E-17 cg25953350 chrll 45167368 0.26 8.458E-17 cg20129082 chrll 19736150 0.25 6.255E-16 cg07729130 chrll 45167493 0.22 1.199E-15 cg25451249 chrll 19736241 0.23 7.488E-15 cg26290543 chrll 45377324 0.21 3.161E-21 cg09723979 chrll 19736248 0.25 1.272E-15 cg02364610 chrll 46317036 0.22 4.98E-22 cg24565274 chrll 19736253 0.25 9.642E-15 cgl4547067 chrll 46317154 0.32 9.372E-18

_

cg03131732 chrll 46317475 0.26 1.916E-23 cgl9885625 chrll 64815313 0.22 9.002E-17 cg09896120 chrll 46317577 0.21 1.932E-22 cg08965235 chrll 65325158 0.25 1.103E-21 cg21770622 chrll 46383066 0.26 5.686E-24 cgl6477774 chrll 65325249 0.24 2.159E-18 cg02865822 chrll 46383141 0.22 2.873E-23 cg06065225 chrll 65640137 0.21 3.436E-14 cgl8337963 chrll 46383209 0.20 4.248E-20 cg24960947 chrll 65816463 0.20 9.814E-16 cg09242181 chrll 46940517 0.23 2.074E-23 cg07145284 chrll 66084631 0.24 1.564E-16 cg08300419 chrll 47208959 0.35 2.746E-19 cgl3383058 chrll 66084660 0.21 7.715E-18 cg24779587 chrll 47209163 0.25 3.321E-23 cg05475524 chrll 66326798 0.24 2.41E-14 cg04959790 chrll 47278977 0.20 1.256E-16 cg05116382 chrll 66327000 0.21 1.293E-14 cg07298473 chrll 47279183 0.27 7.784E-24 cg05743713 chrll 66885240 0.27 1.443E-20 cg00536939 chrll 47279352 0.29 7.633E-21 cg04434593 chrll 67139546 0.26 3.032E-20 cg08690459 chrll 47279586 0.21 1.227E-23 cg02659086 chrll 67350976 0.26 2.244E-19 cg26197915 chrll 48085137 0.21 1.646E-20 cg04920951 chrll 67351271 0.28 2.01E-19 cgll751645 chrll 56947754 0.24 1.5E-15 cg26250609 chrll 67351273 0.26 1.025E-19 cg00522883 chrll 57194120 0.26 8.054E-24 cg06928838 chrll 67351490 0.29 IE-23 cg07067982 chrll 57194370 0.31 3.405E-24 cg09038676 chrll 67351608 0.33 3.446E-22 cgl9167683 chrll 57194495 0.23 3.56E-20 cgll566244 chrll 67351786 0.31 1.907E-22 cg07326438 chrll 57194562 0.32 5.536E-17 cgll096993 chrll 67417958 0.20 1.169E-18 cg00264441 chrll 57250469 0.38 3.126E-25 cgl2894325 chrll 67418113 0.22 2.834E-18 cg08498787 chrll 57250780 0.37 5.596E-26 cg23740940 chrll 68924746 0.23 6.901E-23 cgl2783776 chrll 57365948 0.24 5.474E-22 cg03469862 chrll 68924853 0.27 3.583E-21 cg20907456 chrll 57405372 0.23 8.195E-24 cg09177106 chrll 69451645 0.24 5.109E-15 cg05415131 chrll 58940866 0.41 3.507E-25 cgl0784570 chrll 69452398 0.20 2.386E-14 cgl4329059 chrll 58940964 0.31 1.073E-26 cg20014822 chrll 69517103 0.23 4.482E-17 cgl7696194 chrll 58941051 0.29 1.421E-22 cgll207763 chrll 69517471 0.21 4.347E-14 cg07745373 chrll 58941415 0.21 9.271E-23 cg04396791 chrll 70508180 0.22 6.395E-18 cg24158259 chrll 58984544 0.25 1.222E-19 cg03395558 chrll 70508329 0.25 2.245E-17 cg26090107 chrll 60718882 0.23 1.035E-15 cgl7627654 chrll 70508410 0.22 2.5E-18 cg06282270 chrll 61062910 0.31 3.037E-14 cg06223539 chrll 70517374 0.22 4.121E-17 cg01698298 chrll 61062964 0.24 3.823E-14 cg04505435 chrll 70672511 0.31 3.227E-19 cg02674352 chrll 61275826 0.21 9.853E-15 cg09448677 chrll 70672740 0.24 2.317E-21 cg06405186 chrll 61283968 0.30 4.669E-22 cg01655356 chrll 70672841 0.23 1.283E-21 cgl0442157 chrll 61284134 0.26 2.098E-22 cg04262428 chrll 70673256 0.20 3.898E-21 cg08752135 chrll 61284417 0.21 3.429E-22 cg21593030 chrll 70952175 0.20 3.957E-15 cgl6105461 chrll 61485853 0.21 1.652E-19 cg03567358 chrll 71050535 0.24 2.575E-23 cg07005513 chrll 61595956 0.21 3.777E-19 cg08876932 chrll 71955547 0.23 4.202E-19 cgl0868875 chrll 61596307 0.28 2.105E-22 cg24530250 chrll 71955599 0.27 3.075E-19 cgl9610905 chrll 61596333 0.28 7.301 E-25 cg04574090 chrll 74178749 0.20 3.144E-14 cg26330416 chrll 62691066 0.23 5.387E-21 cgl3430464 chrll 74408131 0.21 2.737E-21 cg23452969 chrll 62691182 0.28 5.587E-18 cgl9225602 chrll 75269316 0.22 6.078E-19 cg04557452 chrll 62691251 0.29 2.933E-19 cg05774229 chrll 76033097 0.27 3.452E-18 cg22358236 chrll 62691452 0.22 2.667E-19 cgl8395917 chrll 76033367 0.33 7.119E-23 cg09952395 chrll 63258712 0.29 1.529E-17 cgl9818890 chrll 76033391 0.23 9.132E-23 cg23728669 chrll 63258734 0.22 2.904E-17 cg05476483 chrll 76750693 0.21 3.46E-15 cgl3112361 chrll 63258739 0.21 1.734E-17 cg20852226 chrll 76859010 0.27 2.054E-18 cg22250498 chrll 63258744 0.23 6.606E-17 cg08879470 chrll 76859056 0.30 1.461E-16 cg22380508 chrll 63381144 0.23 8.783E-16 cg08481002 chrll 78131601 0.26 9.279E-20 cg04986616 chrll 63537378 0.30 9.391E-21 cg02973171 chrll 82443614 0.26 2.413E-16 cg09907758 chrll 63537459 0.26 1.336E-22 cgl7524136 chrll 84028382 0.22 1.643E-22 cg22796860 chrll 63828346 0.29 2.476E-23 cgl8121003 chrll 86085757 0.24 5.339E-18 cg03103218 chrll 63828672 0.25 1.157E-17 cg02094273 chrll 86636018 0.21 7.663E-22 cg09908110 chrll 63828713 0.30 2.201E-19 cgll670211 chrll 89224288 0.25 4.414E-20 cg01566127 chrll 63828762 0.21 8.254E-19 cgl2161228 chrll 89224506 0.32 8.091E-18 cg03784628 chrll 64059937 0.20 2.456E-18 cg03793270 chrll 89224684 0.25 5.211E-18 cgl9917412 chrll 64815189 0.24 1.047E-17 cgl7063929 chrll 89224799 0.21 3.602E-19

cg23792314 chrl2 25056243 0.22 4.935E-18 cg07007400 chrl2 52626831 0.22 2.569E-17 cg25451893 chrl2 25538177 0.27 8.013E-23 cgl4482313 chrl2 52626889 0.22 1.749E-14 cgl3910046 chrl2 25538221 0.27 1.823E-22 cgl4537533 chrl2 52626904 0.21 2.52E-14 cg25572367 chrl2 25538380 0.20 1.466E-15 cg22193385 chrl2 52638005 0.21 1.938E-20 cg04100595 chrl2 27615138 0.21 3.704E-18 cg02305765 chrl2 53107910 0.26 9.772E-18 cgll390073 chrl2 29302515 0.22 1.196E-20 cg08691567 chrl2 53183930 0.25 4.281E-18 cgl5885440 chrl2 29302714 0.25 1.001E-21 cg01492330 chrl2 53184005 0.29 1.58E-16 cgl4258853 chrl2 29935411 0.26 1.576E-15 cgl3885357 chrl2 53184041 0.39 1.433E-16 cgl0512875 chrl2 29936174 0.26 2.898E-19 cgl5608277 chrl2 53184086 0.30 6.036E-16 cgl2064372 chrl2 30948792 0.25 4.299E-15 cg02303897 chrl2 53268136 0.25 6.012E-17 cgl9540425 chrl2 32655836 0.25 9.376E-22 cgl7419626 chrl2 53268268 0.22 4.043E-22 cgl3519035 chrl2 34261006 0.24 4.719E-19 cg05393297 chrl2 53359155 0.22 3.669E-17 cgl4497054 chrl2 34261116 0.21 1.422E-16 cg25025879 chrl2 53359317 0.26 2.591E-19 cgll684647 chrl2 40618356 0.20 1.512E-18 cgl6329197 chrl2 53359506 0.24 4.802E-20 cgl4243778 chrl2 41086879 0.24 5.29E-18 cgl3937905 chrl2 53612551 0.21 3.47E-19 cgl9034038 chrl2 45443996 0.22 1.125E-20 cgl0592478 chrl2 53612641 0.29 1.06E-21 cgl2686055 chrl2 45628262 0.20 1.099E-21 cg09107344 chrl2 53612734 0.25 2.179E-22 cg04923020 chrl2 46005007 0.22 7.065E-25 cg20059012 chrl2 53613154 0.32 2.309E-20 cgl4239655 chrl2 46005115 0.28 1.156E-24 eg 13940444 chrl2 53617382 0.30 6.91E-21 cg26724975 chrl2 46554412 0.21 8.371E-22 cgl6331883 chrl2 53886170 0.22 6.066E-21 cg20408693 chrl2 46767289 0.22 6.264E-16 cg25810484 chrl2 54089486 0.22 8.287E-16 cg04053798 chrl2 47219705 0.20 4.689E-16 cgll560280 chrl2 54089497 0.23 9.981E-15 cglll46691 chrl2 47219737 0.32 2.056E-16 cg23533419 chrl2 54090519 0.20 1.916E-22 cgl7501823 chrl2 47219793 0.26 5.359E-17 cg00028308 chrl2 54090754 0.22 4.044E-16 cg21428710 chrl2 47219797 0.22 1.575E-18 cgl3990926 chrl2 54133447 0.30 2.032E-16 cg07601320 chrl2 47219841 0.22 1.849E-16 cgl4950169 chrl2 54145841 0.29 1.874E-16 cgll331445 chrl2 47219877 0.24 8.856E-16 cg08190858 chrl2 54321346 0.29 4.907E-18 cg22868282 chrl2 47224954 0.21 8.246E-15 cg07915921 chrl2 54321502 0.26 8.451E-15 cg08135379 chrl2 47474763 0.23 2.666E-15 cg21707187 chrl2 54345862 0.26 9.076E-15 cgl6266579 chrl2 48591673 0.31 1.011E-17 cg05516489 chrl2 54359761 0.20 1.373E-14 cg26205652 chrl2 48591994 0.37 4.67E-16 cg00079219 chrl2 54360131 0.22 6.049E-18 cg08184792 chrl2 48592270 0.30 1.011E-19 cg03132556 chrl2 54366760 0.24 2.151E-14 cgl4121142 chrl2 49391363 0.20 4.482E-17 cg08962452 chrl2 54366816 0.22 8.881E-16 cg05140648 chrl2 49391920 0.25 2.175E-21 cg22709192 chrl2 54366909 0.22 1.132E-17 cgl5661753 chrl2 49627010 0.23 1.599E-17 cg03536474 chrl2 54367460 0.21 2.331E-14 cg09049251 chrl2 50297477 0.21 1.766E-15 cg09887284 chrl2 54388147 0.20 1.135E-15 cg27188703 chrl2 50297581 0.29 7.894E-19 cg24208826 chrl2 54389891 0.27 3.61E-16 cgl6115588 chrl2 50297588 0.28 5.842E-20 cgl3545297 chrl2 54404315 0.21 1.256E-19 cgl8486102 chrl2 50297777 0.32 5.361E-19 cg03078363 chrl2 54408664 0.35 4.952E-27 cg06947913 chrl2 50297793 0.35 2.978E-21 cg04105511 chrl2 54409207 0.20 1.449E-16 cg04669574 chrl2 50297945 0.22 1.893E-19 cg26019295 chrl2 54409212 0.22 1.322E-16 cg08266366 chrl2 50354998 0.29 3.162E-22 cg01473837 chrl2 54409321 0.21 7.831E-17 cgl5336765 chrl2 50355307 0.34 1.95E-18 cgl6937769 chrl2 54409485 0.25 7.996E-22 cgl3490422 chrl2 50377731 0.25 6.587E-23 cg04704531 chrl2 54409491 0.28 3.117E-23 cgl9604907 chrl2 50444723 0.20 4.45E-17 cg06714180 chrl2 54409525 0.30 8.973E-18 cg23497020 chrl2 50616562 0.27 1.183E-21 cgl5817960 chrl2 54409599 0.23 5.878E-16 cgl2439325 chrl2 51236768 0.21 5.917E-19 cgl3726459 chrl2 54409657 0.22 2.349E-21 cg20092892 chrl2 52258077 0.20 9.465E-15 cg07080050 chrl2 54413345 0.20 3.969E-15 cg02392696 chrl2 52258264 0.23 1.655E-15 cg03892356 chrl2 54420837 0.30 3.537E-21 cg04034767 chrl2 52400907 0.32 5.286E-18 cg00506343 chrl2 54421033 0.23 8.296E-24 cg00817367 chrl2 52401214 0.38 3.39E-25 cg23618344 chrl2 54423428 0.32 1.246E-18 cg06970510 chrl2 52401448 0.31 2.434E-19 cg23697546 chrl2 54424085 0.28 8.357E-18 cgl5994467 chrl2 52401523 0.26 7.727E-20 cgl3826247 chrl2 54424203 0.21 3.723E-18 cg07967679 chrl2 52626814 0.23 5.175E-18 cg00040312 chrl2 54424679 0.24 1.949E-20 cg08975803 chrl2 52626818 0.22 5.444E-20 cgl8054172 chrl2 54424902 0.21 2.574E-18

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cgl0005224 chrl2 54424964 0.22 2.304E-18 cg03188000 chrl2 68634913 0.22 6.763E-18 cg21041775 chrl2 54425418 0.21 3.513E-18 cg02544037 chrl2 68759069 0.21 4.446E-17 cg00218447 chrl2 54428171 0.27 1.446E-18 cg24234651 chrl2 75728471 0.22 1.953E-16 cg21216477 chrl2 54440773 0.22 5.554E-20 cg23520422 chrl2 76423956 0.25 2.784E-20 cg08465346 chrl2 54441458 0.26 2.061E-19 cg05854114 chrl2 77719408 0.24 3.357E-14 cg22151644 chrl2 54444047 0.20 4.244E-19 cg05860723 chrl2 81102486 0.21 5.105E-19 cgll594833 chrl2 54444985 0.20 4.357E-16 cg00354572 chrl2 81471419 0.21 1.168E-17 cgl8695839 chrl2 54446944 0.26 3.511E-19 cg25971727 chrl2 81471533 0.22 4.214E-16 cgl8922524 chrl2 54447136 0.20 4.477E-20 cg21754400 chrl2 81471649 0.24 7.529E-16 cg03923561 chrl2 54447220 0.31 1.452E-23 cgll659501 chrl2 81471678 0.29 3.701E-18 cg02264990 chrl2 54447243 0.31 6.772E-25 cg23614791 chrl2 81471754 0.23 1.65E-14 cg09720701 chrl2 54447283 0.24 1.615E-20 cg25358039 chrl2 81471757 0.23 1.975E-14 cgl5233062 chrl2 54447349 0.29 1.783E-21 cgl3273396 chrl2 81471867 0.31 1.93E-17 cgll585893 chrl2 54447430 0.20 4.291E-18 cg24711649 chrl2 81472118 0.23 3.064E-16 cg07266404 chrl2 54447584 0.29 9.541E-23 cgl0866060 chrl2 83592588 0.23 4.602E-22 cgl5894722 chrl2 54447596 0.23 2.307E-18 cgl6733705 chrl2 85667616 0.22 7.898E-17 cg01524853 chrl2 54447807 0.23 1.328E-23 cgl3916459 chrl2 85673221 0.32 1.641E-19 cg22747076 chrl2 54447873 0.38 7.037E-24 cgl4996220 chrl2 85673270 0.20 1.246E-21 cgll746813 chrl2 54448090 0.23 2.308E-20 cg25281029 chrl2 88969462 0.21 1.148E-21 cg03146625 chrl2 54448729 0.20 5.837E-18 cg00772407 chrl2 89744471 0.22 3.423E-20 cg23489434 chrl2 54500175 0.28 5.286E-22 cg07239716 chrl2 89744488 0.23 6.611E-25 cgll306441 chrl2 54520919 0.31 5.3E-18 cg01814191 chrl2 89744524 0.23 1.622E-23 cg27408285 chrl2 54653364 0.31 1.669E-23 cgl7740822 chrl2 89744609 0.21 1.77E-23 cg23824801 chrl2 54653403 0.29 5.619E-24 cg25124406 chrl2 89744662 0.27 1.49E-21 cg20687242 chrl2 54653427 0.27 2.506E-20 cg05769889 chrl2 89744701 0.36 8.094E-28 cg20474425 chrl2 54746067 0.23 2.573E-22 cg01242903 chrl2 89744877 0.24 3.715E-21 cg23795217 chrl2 54812000 0.23 3.302E-15 cg25006194 chrl2 94288553 0.28 1.69E-22 cg03826594 chrl2 54812085 0.23 2.505E-14 cg07533511 chrl2 94580931 0.21 2.79E-22 cg24725263 chrl2 56101328 0.26 1.374E-20 cg23982858 chrl2 95941869 0.27 5.743E-22 cg04850731 chrl2 57618943 0.20 6.104E-17 cg00927554 chrl2 95941920 0.31 1.191E-20 cg01708411 chrl2 57631839 0.22 1.204E-15 cg22538054 chrl2 95941988 0.39 2.393E-20 cgl3212283 chrl2 57632120 0.24 8.945 E- 20 cg26584545 chrl2 96183197 0.21 6.474E-15 cg04270799 chrl2 57944059 0.21 1.134E-19 cg08113245 chrl2 96252176 0.20 3.869E-17 cg01644731 chrl2 58236712 0.21 1.344E-17 cg26911787 chrl2 96587734 0.26 1.826E-14 cg25707722 chrl2 63025490 0.25 1.081E-16 cg07130150 chrl2 96883863 0.22 8.709E-18 cglll55687 chrl2 63025589 0.28 1.826E-15 cg08993878 chrl2 98151379 0.21 2.303E-19 cg08244085 chrl2 63025730 0.30 1.277E-16 cg09831105 chrl2 99287469 0.21 6.092E-19 cg26386409 chrl2 63025771 0.28 7.039E-16 cg21961771 chrl2 100750652 0.24 2.05E-23 cgl5916192 chrl2 63025948 0.26 4.588E-15 cgl4077898 chrl2 100750695 0.28 6.321E-25 cg01804193 chrl2 63026212 0.26 1.258E-14 cg24446178 chrl2 100750702 0.24 2.695E-23 cg09266771 chrl2 63207138 0.24 4.881E-23 cg06563300 chrl2 100750811 0.29 2.725E-23 cg01643123 chrl2 63207179 0.37 4.15E-23 cg21429394 chrl2 100750899 0.21 1.936E-24 cg27454064 chrl2 64215611 0.21 2.658E-21 cg26833652 chrl2 102036256 0.21 5.415E-17 cg22510727 chrl2 64541117 0.24 2.231E-24 cg23891273 chrl2 102036400 0.26 6.556E-15 cg23013309 chrl2 65218841 0.31 5.966E-19 cg27117792 chrl2 102330180 0.22 3.821E-21 cg08815398 chrl2 65218869 0.23 4.901E-18 cg24676120 chrl2 102821557 0.22 3.642E-23 cg06234063 chrl2 65219392 0.27 5.073E-26 cg06652329 chrl2 102874566 0.22 4.104E-18 cg09486902 chrl2 65219478 0.32 1.973E-25 cgl6085568 chrl2 103311088 0.22 6.949E-16 cg06092265 chrl2 65219655 0.24 6.376E-26 cg21490980 chrl2 103311138 0.25 2.622E-16 cgl6355305 chrl2 65220152 0.25 1.719E-25 cgl5963417 chrl2 103311300 0.34 2.06E-17 cg00592781 chrl2 66122874 0.22 4.069E-18 cg24759821 chrl2 103311462 0.24 3.017E-17 cgl0083898 chrl2 66123380 0.21 1.021E-16 cgl8919225 chrl2 103311494 0.26 1.934E-18 cgl5394142 chrl2 66275988 0.23 2.812E-16 cg24167314 chrl2 103311500 0.30 1.725E-18 cg26279550 chrl2 66582805 0.20 6.01E-16 cgl6188209 chrl2 103311596 0.22 4.542E-15 cg20162652 chrl2 66629018 0.32 1.92E-15 cgl8827332 chrl2 103344506 0.21 5.149E-22

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cgl5205636 chrl3 21520468 0.21 2.245E-15 cg20483324 chrl3 46189838 0.26 1.611E-18 cgl8252616 chrl3 22243392 0.23 5.845E-20 cgl7241776 chrl3 51417469 0.30 5.892E-18 cg06001519 chrl3 23500838 0.28 1.278E-19 cg20170533 chrl3 51417846 0.22 1.37E-15 cg04865180 chrl3 23734385 0.25 1.492E-16 cg09557313 chrl3 53313174 0.24 1.638E-18 cg09076334 chrl3 24477870 0.29 9.833E-23 cg08567279 chrl3 53313529 0.24 3.074E-14 cg09473359 chrl3 24477933 0.20 7.416E-19 cg00708598 chrl3 53313895 0.21 1.399E-16 cgl7537073 chrl3 24902500 0.31 3.291E-17 cg23004758 chrl3 58204221 0.20 2.106E-16 cg00742920 chrl3 27050512 0.21 1.014E-16 cg20634967 chrl3 58204224 0.24 2.973E-14 cgl9005168 chrl3 27092836 0.22 4.834E-24 cg25514273 chrl3 70681804 0.24 3.296E-19 cgl3799919 chrl3 28212848 0.22 6.165E-20 cg20523861 chrl3 70682324 0.26 7.281E-20 cg02807859 chrl3 28350407 0.22 5.758E-17 cg20658100 chrl3 74707145 0.26 2.19E-23 cg02067712 chrl3 28364724 0.21 1.261E-19 cgl3696283 chrl3 74707153 0.33 4.607E-23 cg05967403 chrl3 28367245 0.20 2.352E-18 cg26419656 chrl3 74707400 0.28 5.458E-21 cg26299169 chrl3 28498956 0.25 3.456E-15 cg23619399 chrl3 79169753 0.22 1.683E-18 cg00889398 chrl3 28502089 0.24 1.437E-19 cg26132774 chrl3 79170146 0.27 3.16E-17 cg22396555 chrl3 28502461 0.22 1.212E-20 cg24221648 chrl3 79170283 0.22 2.423E-17 cg21963436 chrl3 28541142 0.21 6.575E-16 cgl5126179 chrl3 79181338 0.21 1.164E-16 cg26677584 chrl3 28541468 0.26 8.191E-19 cg22369786 chrl3 80911626 0.27 5.044E-18 cgl2440549 chrl3 28541477 0.28 5.318E-19 cgl3054007 chrl3 81018323 -0.22 3.077E-22 cg07984133 chrl3 28544592 0.26 5.027E-18 cg07104706 chrl3 84456127 0.20 1.401E-14 cgl6201038 chrl3 28544760 0.23 6.531E-17 cglll34334 chrl3 94822726 0.21 6.339E-24 cgl2634080 chrl3 28549922 0.21 1.246E-16 cg01470551 chrl3 95620874 0.33 1.245E-22 cg03465513 chrl3 28550046 0.22 6.154E-17 cg26163458 chrl3 95620976 0.25 2.108E-18 cg23558002 chrl3 28553501 0.20 2.914E-15 cgl8107232 chrl3 95620997 0.28 1.293E-20 cg08380556 chrl3 31020218 0.21 6.182E-16 cgl6232183 chrl3 96204854 0.26 2.73E-17 cgl7180284 chrl3 31783983 0.22 1.642E-21 cg06428163 chrl3 96204856 0.24 2.591E-15 cg01373189 chrl3 33002820 0.25 4.301 E-27 cg04603730 chrl3 96204870 0.27 5.24E-15 cg00944193 chrl3 36044860 0.21 1.194E-17 cg09469554 chrl3 96204917 0.29 9.198E-17 cg07200348 chrl3 36045201 0.21 2.55E-15 cg25032595 chrl3 96204978 0.31 3.315E-16 cg00762613 chrl3 36045224 0.21 1.127E-14 cgl6556145 chrl3 96205184 0.23 3.382E-15 cgl2638731 chrl3 36045281 0.24 2.569E-18 cgl8393747 chrl3 96205295 0.24 6.176E-16 cgl8282455 chrl3 36729109 0.24 1.139E-21 cgl9647813 chrl3 96296144 0.24 1.945E-25 cgl6068263 chrl3 36729231 0.26 3.455E-21 cg00158308 chrl3 97646341 0.31 7.517E-23 cgl0558887 chrl3 36919409 0.25 1.371E-17 cg03371199 chrl3 97646639 0.21 8.475E-15 cg20691205 chrl3 36919674 0.25 8.389E-20 cgl3990092 chrl3 97646731 0.27 4.982E-14 cg03966514 chrl3 36919738 0.31 1.137E-17 cg22996489 chrl3 97646736 0.27 4.106E-14 cg01404317 chrl3 36919819 0.30 6.595E-21 cgl8956714 chrl3 97646803 0.21 1.91E-15 cgl8755783 chrl3 36919905 0.28 1.182E-17 cg23037133 chrl3 97646811 0.22 1.347E-16 cg00947032 chrl3 36919960 0.30 1.5E-19 cg24663970 chrl3 97647084 0.27 6.227E-17 cgl3060997 chrl3 37006611 0.21 4.259E-15 cg00221494 chrl3 98794593 0.23 1.07E-16 cg25217100 chrl3 37249426 0.22 2.103E-17 cg05621157 chrl3 99404279 0.23 9.471E-16 cg21476299 chrl3 43148214 0.20 1.233E-17 cgl4684709 chrl3 100547249 0.26 1.73E-14 cg00880018 chrl3 43149171 0.23 1.415E-16 cg00743094 chrl3 100547968 0.26 1.236E-15 cg25261228 chrl3 43566114 0.22 1.603E-14 cg07931391 chrl3 100608263 0.35 7.787E-16 cgl4539231 chrl3 43566262 0.28 1.174E-15 cg04579493 chrl3 100609947 0.25 2.594E-16 cg00338116 chrl3 43566313 0.23 1.801E-15 cgl8557131 chrl3 100624207 0.22 9.955E-16 cg22905097 chrl3 43566401 0.28 2.526E-15 cgl6033633 chrl3 100624855 0.20 3.782E-17 cgl9915711 chrl3 43566421 0.32 5.194E-17 cg21100077 chrl3 100627366 0.20 5.417E-16 cg22125968 chrl3 43566472 0.31 8.444E-15 cgl8161327 chrl3 100627703 0.25 1.339E-18 cg01536987 chrl3 43566492 0.30 4.499E-15 cg20374595 chrl3 100627956 0.23 7.28E-22 cgl8882819 chrl3 43566496 0.27 8.11E-16 cgl7882660 chrl3 100637258 0.22 3.89E-14 cg03478249 chrl3 43566547 0.28 1.249E-15 cg00295794 chrl3 100641409 0.31 2.209E-17 cgl2138678 chrl3 43566618 0.24 4.147E-18 cgl8008019 chrl3 100641646 0.23 6.662E-20 cg04308040 chrl3 44942303 0.23 4.595E-21 cg25334575 chrl3 100641744 0.24 1.105E-18 cg06807397 chrl3 44948413 0.23 1.165E-20 cgl9385331 chrl3 100641867 0.23 1.096E-18

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cgl2821539 chrl3 100642775 0.25 2.646E-16 cgl8454133 chrl4 23835870 0.27 2.53E-23 cgl2438547 chrl3 100642971 0.21 9.243E-17 cg07197059 chrl4 23836012 0.23 7.804E-20 cg04370314 chrl3 100643312 0.25 2.044 E- 15 cg26206183 chrl4 24457993 0.30 1.678E-15 cg22489321 chrl3 100643388 0.27 6.939E-21 cgl3555354 chrl4 24458014 0.36 2.218E-15 cgl3436155 chrl3 100644217 0.21 1.302E-19 cg01597387 chrl4 24458208 0.24 5.093E-15 cgll694262 chrl3 100644657 0.22 1.204E-14 cgl8556834 chrl4 24641070 0.24 6.196E-21 cg01528028 chrl3 100649800 0.22 2.02E-18 cgl9989295 chrl4 24641077 0.28 6.968E-24 cg25810247 chrl3 108867154 0.23 1.631E-14 cgl8534491 chrl4 24641155 0.23 2.306E-25 cg20945738 chrl3 108922032 0.21 1.185E-20 cg03431846 chrl4 24641183 0.24 1.147E-21 cgl8703238 chrl3 108922361 0.20 1.642E-18 cgl8628371 chrl4 24641189 0.27 7.034E-23 cg09450063 chrl3 108922504 0.21 7.394E-21 cgl6425038 chrl4 24641194 0.31 9.205E-22 cgl5292275 chrl3 109149011 0.26 5.964E-19 cg07516252 chrl4 24641201 0.22 1.357E-20 cg07647726 chrl3 109149171 0.26 3.692E-21 cg07485357 chrl4 24803679 0.20 1.114E-17 cg09168153 chrl3 110779117 0.20 9.797E-21 cgl6761581 chrl4 24803807 0.30 1.44E-20 cg07502829 chrl3 112708288 0.21 1.426E-18 cg23179456 chrl4 24803873 0.39 1.242E-19 cg09797337 chrl3 112709538 0.23 2.569E-15 cgl3631572 chrl4 24803903 0.24 1.968E-21 cg23619365 chrl3 112712009 0.27 3.648E-15 cgl6215203 chrl4 24803917 0.28 3.258E-22 cg03276408 chrl3 112712475 0.20 3.117E-19 cg25556905 chrl4 24803925 0.38 2.375E-22 cg26751356 chrl3 112712635 0.23 2.299E-17 cgl2265829 chrl4 24804022 0.30 2.376E-20 cgl6705627 chrl3 112721950 0.26 9.052E-18 cg05031016 chrl4 24804153 0.28 2.733E-20 cgl5415452 chrl3 112759355 0.22 2.762E-16 cgl4287235 chrl4 24804339 0.32 1.467E-23 cgl3692446 chrl3 112759719 0.20 1.159E-16 cgl9646112 chrl4 24804342 0.26 3.509E-22 cgl7296589 chrl3 113366074 0.23 1.502E-18 cgl3066043 chrl4 24808987 0.25 6.152E-19 cgl9028462 chrl3 113677628 0.21 5.689E-17 cg20822579 chrl4 24809073 0.21 6.485E-19 cg09714458 chrl3 113807560 0.25 3.688E-15 cgl2177793 chrl4 24837892 0.30 2.968E-19 cgl6820615 chrl3 114884918 0.22 8.079E-16 cg26009486 chrl4 24838008 0.24 1.012E-22 cgll570367 chrl3 114896683 0.30 1.529E-15 cg01233722 chrl4 24838126 0.22 2.578E-17 cg26786795 chrl4 20344394 0.25 7.089E-22 cg08282145 chrl4 24868755 0.21 8.619E-24 cgl4262740 chrl4 20612220 0.21 3.491E-19 cg08273957 chrl4 29227941 0.22 4.769E-17 cg02852670 chrl4 20903410 0.23 4.5 E- 20 cg07974473 chrl4 29235092 0.22 6.501E-20 cgl0982443 chrl4 20903611 0.25 1.504E-18 cg23191956 chrl4 29235123 0.24 1.256E-18 cg23552977 chrl4 21492433 0.20 1.243E-19 cg25078444 chrl4 29235193 0.26 3.418E-16 cg20902783 chrl4 21494071 0.26 1.168E-24 cgl6038120 chrl4 29235196 0.25 1.2E-16 cgl8081258 chrl4 21494161 0.26 5.175E-26 cg05872306 chrl4 29236535 0.21 3.066E-16 cgl6082336 chrl4 21539712 0.20 1.956E-17 cg07489048 chrl4 29236898 0.23 1.184E-14 cg26066597 chrl4 21540022 0.28 6.224E-24 cg21195256 chrl4 29244278 0.26 6.161E-15 cgl8575809 chrl4 21540329 0.24 2.214E-21 cg01302656 chrl4 29254853 0.20 2.033E-17 cg00800229 chrl4 22004993 0.33 8.495 E- 24 cgl4006181 chrl4 29254942 0.26 4.1E-21 cg21876626 chrl4 22005045 0.25 9.238E-25 cgll226913 chrl4 29254961 0.23 2.174E-19 cg01897797 chrl4 22005140 0.33 3.223E-25 cg07019438 chrl4 34419546 0.25 2.256E-14 cg22921760 chrl4 22005368 0.21 1.566E-25 cg25027125 chrl4 35182801 0.20 6.811E-20 cgl6304521 chrl4 22191827 0.21 2.1E-19 cg08086724 chrl4 36973204 0.22 3.682E-18 cgl9846667 chrl4 22191856 0.23 3.284E-18 cgl3209481 chrl4 36973483 0.23 5.863E-17 cg01508380 chrl4 23305585 0.23 3.792E-17 cgl3012916 chrl4 36973691 0.26 7.599E-17 cgl0418289 chrl4 23308294 0.21 4.261E-22 cg23929344 chrl4 36975402 0.20 1.166E-15 cgl4920289 chrl4 23821149 0.21 1.118E-14 cgl4112075 chrl4 36977818 0.20 4.175E-16 cgl7199325 chrl4 23821229 0.22 3.783E-14 cg20000562 chrl4 36978633 0.23 1.499E-19 cgl7606785 chrl4 23834808 0.22 3.852E-17 cg04926361 chrl4 36982447 0.23 1.558E-20 cgll840125 chrl4 23834860 0.22 1.968E-17 cg27294268 chrl4 36983518 0.22 6.789E-17 cgl3011388 chrl4 23834909 0.29 9.452E-15 cg05372242 chrl4 36983542 0.22 3.367E-17 cgl8844382 chrl4 23834977 0.31 5.868E-19 cg04330513 chrl4 36983694 0.24 3.074E-16 cg21013866 chrl4 23834985 0.31 3.385E-15 cg09307564 chrl4 36983737 0.23 2.112E-18 cg02213260 chrl4 23834995 0.21 3.308E-19 cg07345734 chrl4 36986363 0.26 3.908E-15 cgl6585972 chrl4 23835212 0.25 5.538E-18 cg23906738 chrl4 36987301 0.25 9.7E-15 cgl7205324 chrl4 23835595 0.23 5.964E-24 cg01630690 chrl4 36992001 0.25 1.914E-18

cg04224064 chrl4 36992233 0.34 2.441E-21 cg05315321 chrl4 68844276 0.24 1.037E-23 cgl8468354 chrl4 36993517 0.23 3.229E-17 cgl0968631 chrl4 69986021 0.20 4.784E-21 cg01075271 chrl4 38080314 0.20 8.885E-17 cgl6565031 chrl4 70186289 0.20 8.903E-20 cg23248887 chrl4 38679643 0.32 9.899E-19 cgl6709294 chrl4 70235567 -0.23 2.957E-21 cg07471943 chrl4 38679656 0.20 2.051E-18 cgl0848272 chrl4 70653719 0.24 2.088E-19 cg04265797 chrl4 38679952 0.20 2.577E-18 cg00890485 chrl4 70653919 0.32 1.406E-23 cg04573550 chrl4 38680313 0.25 4.642E-19 cg23241781 chrl4 70653964 0.37 4.487E-22 cgl6190266 chrl4 38680855 0.24 1.53E-19 cgl9545232 chrl4 70654247 0.28 6.487E-24 cgl6404157 chrl4 38724648 0.27 5.486E-17 cg01646639 chrl4 70654290 0.21 1.108E-20 cg05057720 chrl4 38724675 0.33 2.879E-18 cg02058870 chrl4 72053146 0.26 5.135E-19 cg23288059 chrl4 38724945 0.21 1.537E-20 cg09636214 chrl4 73712491 0.22 4.993E-18 cgl0996258 chrl4 38975251 0.21 2.994E-20 cgl5416329 chrl4 74706016 0.24 2.674E-20 cgl0327400 chrl4 42075406 0.20 3.813E-18 cg07573727 chrl4 74706196 0.24 1.356E-21 cg02454806 chrl4 42075554 0.23 3.407E-21 cg27317046 chrl4 74968209 0.24 1.555E-16 cgl8856581 chrl4 48145000 0.21 3.746E-15 cgl0101773 chrl4 75894136 0.32 3.283E-22 cg05309989 chrl4 50527872 0.26 6.76E-24 cg02114084 chrl4 75894209 0.21 4.156E-21 cg08572565 chrl4 51298737 0.21 2.398E-16 cgl8322546 chrl4 77422738 0.23 1.762E-22 cg01270593 chrl4 51339072 0.20 1.448E-16 cgl6324314 chrl4 77480847 0.22 1.014E-19 cgl7347389 chrl4 51562646 0.22 4.872E-17 cgl3038685 chrl4 77504478 0.24 3.842E-23 cg21929473 chrl4 51862102 0.20 1.543E-22 cg22930859 chrl4 78108189 0.22 7.038E-19 cg09841842 chrl4 51974848 0.27 6.275E-24 cgl3833923 chrl4 79746627 0.22 2.235E-16 cg04701034 chrl4 52536175 0.24 1.441E-14 cg01537995 chrl4 85996352 0.27 5.508E-22 cgl6695483 chrl4 52536436 0.21 4.659E-14 cgl6800165 chrl4 85996364 0.27 8.221E-23 cg20297199 chrl4 54422775 0.23 2.498E-16 cgl7410236 chrl4 85996495 0.25 8.65E-17 cg08162372 chrl4 54422925 0.27 1.591E-16 cg01711160 chrl4 85996499 0.27 2.953E-19 cgl6379462 chrl4 55119082 0.24 1.393E-19 cgl8070676 chrl4 85997519 0.28 6.081E-22 cg00107772 chrl4 57261886 0.25 2.574E-18 cg03506640 chrl4 85997753 0.23 1.367E-17 cg08235161 chrl4 57262049 0.25 1.63E-20 cgl8103730 chrl4 88458917 0.20 1.01E-17 cg21106407 chrl4 57262177 0.28 1.646E-20 cg07072475 chrl4 90850234 0.20 1.262E-14 cg02237629 chrl4 57264095 0.24 4.474E-19 cg06907680 chrl4 91580129 0.23 9.38E-18 cgl9871940 chrl4 57264287 0.31 4.018E-18 cg26288577 chrl4 91580429 0.26 8.063E-16 cgl8479593 chrl4 57265560 0.24 2.703E-16 cgl3186286 chrl4 91580451 0.22 8.298E-15 cg27122213 chrl4 57274763 0.22 1.178E-17 cgl8639180 chrl4 91580605 0.23 2.84E-15 cgl3023623 chrl4 57276257 0.26 2.297E-17 cg23296408 chrl4 91580613 0.24 7.347E-15 cg06966811 chrl4 57276789 0.20 1.441E-20 cg07063068 chrl4 91711033 0.21 5.757E-18 cgl6793394 chrl4 57278084 0.20 5.368E-16 cgl0497871 chrl4 92041114 0.20 1.098E-16 cgl8451814 chrl4 57278188 0.23 2.361E-18 cg07575518 chrl4 92413497 0.27 7.876E-20 cg09624466 chrl4 57278710 0.24 1.686E-15 cg21883802 chrl4 92413706 0.30 3.436E-17 cg21039708 chrl4 57278729 0.31 5.797E-16 cgl9767131 chrl4 92979698 0.24 1.252E-17 cg25092838 chrl4 57279115 0.24 3.074E-14 cgl2169365 chrl4 92979709 0.22 2.34E-16 cg04548856 chrl4 57284528 0.24 1.564E-20 cg20895877 chrl4 94254586 0.29 3.389E-14 cg21141024 chrl4 59422098 0.22 9.393E-20 cgl0002178 chrl4 94254726 0.35 2.991E-17 cg21026830 chrl4 60973517 0.28 2.088E-16 cgl9630689 chrl4 94984381 0.23 9.849E-23 cgl3539545 chrl4 60973823 0.30 4.932E-18 cgl9904425 chrl4 94984530 0.20 1.107E-19 cg24736989 chrl4 60973904 0.21 3.011E-15 cgl3073773 chrl4 95234658 0.21 1.787E-14 cgl0755235 chrl4 60974039 0.21 2.411E-16 cg23695707 chrl4 95234826 0.20 3.61E-16 cgl9456540 chrl4 60976285 0.21 4.266E-14 cgl8687675 chrl4 95234965 0.21 1.067E-15 cgl2091642 chrl4 61104566 0.23 1.124E-14 cg02948476 chrl4 95235026 0.24 5.528E-17 cg26236177 chrl4 61110649 0.24 1.801E-19 cg01163842 chrl4 95235125 0.30 4.822E-14 cgl4007871 chrl4 61120134 0.24 2.202E-16 cg07785447 chrl4 95235127 0.25 6.394E-15 cgl4272084 chrl4 61685564 0.23 8.1E-18 cg21063282 chrl4 95235402 0.25 8.487E-16 cg01779765 chrl4 62583795 0.26 9.235E-19 cg01533258 chrl4 95235489 0.24 6.079E-15 cgl9841369 chrl4 64663928 0.20 1.89E-20 cg04932340 chrl4 95239381 0.21 1.386E-16 cg21927177 chrl4 65172436 0.26 4.819E-25 cgl9870698 chrl4 95239570 0.27 1.484E-16 cg23373640 chrl4 65696480 0.20 4.721E-18 cg01796166 chrl4 95239586 0.24 6.17E-16

cg08196032 chrl4 95239751 0.23 5.506E-18 cg02779016 chrl5 43809689 0.22 1.437E-21 cgl0746936 chrl4 95240143 0.26 3.424E-19 cgl5159104 chrl5 43809865 0.20 1.332E-20 cgl4943113 chrl4 95240444 0.21 9.942E-17 cg21883598 chrl5 45404157 0.28 1.261E-18 cg24034005 chrl4 97059192 0.27 1.436E-14 cgl2374123 chrl5 45406327 0.20 2.543E-18 cg01683794 chrl4 97059349 0.22 5.946E-19 cgl3899314 chrl5 45406480 0.24 8.21E-17 cgl9567689 chrl4 97059467 0.21 9.152E-18 cg00465476 chrl5 45406486 0.20 1.232E-14 cg04958794 chrl4 97685274 0.21 1.163E-19 cg02454595 chrl5 45406534 0.27 9.912E-17 cg24674368 chrl4 97879637 0.23 5.687E-16 cg00877887 chrl5 45406654 0.23 7.658E-19 cgl2961080 chrl4 99736143 0.24 5.098E-17 cg02550961 chrl5 45406866 0.31 4.383E-19 cg24683041 chrl4 100413076 0.20 2.297E-20 cg04001842 chrl5 45406939 0.20 6.152E-19 cg23997405 chrl4 101033689 0.36 2.532E-28 cgl9968840 chrl5 45409319 0.25 5.816E-18 cg01590338 chrl4 101831332 0.20 1.535E-14 cgl3605988 chrl5 45421612 0.25 1.685E-16 cgl3797425 chrl4 102554977 0.24 1.728E-16 cgl8088242 chrl5 45422325 0.24 1.075E-17 cg25577023 chrl4 103394899 0.21 6.222E-17 cgl8582992 chrl5 45479642 0.40 1.654E-21 cgl5827779 chrl4 103524899 0.28 1.94E-21 cg24033558 chrl5 45479755 0.40 1.707E-16 cg24779941 chrl4 103524901 0.24 1.574E-19 cg24381412 chrl5 45996787 0.22 4.513E-15 cgl8927077 chrl4 103605358 0.26 1.169E-20 cgl0480343 chrl5 48938347 0.24 1.776E-15 cg01363714 chrl4 103655773 0.24 3.449E-16 cg22535307 chrl5 48938370 0.22 2.369E-15 cgl7275781 chrl4 103740085 0.21 1.468E-15 cg08151731 chrl5 48938576 0.24 5.093E-24 cg01121022 chrl4 104338788 0.22 5.074E-15 cg24360909 chrl5 49189538 0.24 2.186E-22 cg21091128 chrl4 104583799 0.26 2.799E-17 cg05905176 chrl5 51385916 0.31 3.726E-17 cgl4361409 chrl4 104584098 0.28 1.635E-14 cg00063471 chrl5 51385970 0.23 1.8E-17 cg06858555 chrl4 105144735 0.21 8.542E-20 cg06813578 chrl5 51386254 0.22 3.246E-17 cg23385208 chrl4 105439913 0.21 2.855E-17 cg22711676 chrl5 53075421 0.23 5.314E-15 cg07193234 chrl5 28341783 0.21 8.665E-20 cg00074145 chrl5 53075505 0.21 3.572E-15 cg09792204 chrl5 28342183 0.27 1.053E-21 cg01663018 chrl5 53097777 0.23 6.06E-15 cgl7741501 chrl5 29077493 0.30 2.905E-18 cg24866923 chrl5 54051239 0.21 3.709E-16 cgl5605858 chrl5 29395932 0.24 5.765E-15 cg08857201 chrl5 56536865 0.21 5.333E-23 cg09077934 chrl5 29407792 0.25 1.237E-22 cgl3578841 chrl5 57719922 0.21 4.821E-21 cgl7716765 chrl5 29407853 0.22 1.417E-19 cg08889009 chrl5 59157123 0.21 4.328E-16 cg20663376 chrl5 31372997 0.21 1.857E-17 cg25489866 chrl5 59729553 0.28 3.866E-16 cg03465028 chrl5 31658323 0.21 4.8E-14 cgl8207741 chrl5 60294120 0.24 9.012E-17 cg02228815 chrl5 31685131 0.21 2.147E-24 cg26517663 chrl5 60295294 0.23 1.2E-17 cgl2134633 chrl5 32934004 0.25 1.137E-18 cg02072495 chrl5 60689285 0.25 3.369E-21 cg09656020 chrl5 33009409 0.20 1.736E-21 cg00930615 chrl5 60690667 0.33 1.924E-22 cgl8145505 chrl5 33009498 0.25 9.445E-18 cg22502206 chrl5 60690826 0.26 3.073E-23 cg03884132 chrl5 33009531 0.26 5.661E-17 cg20118643 chrl5 60690852 0.32 1.554E-24 cg08935118 chrl5 35014229 0.27 5.679E-21 cgll421255 chrl5 60690974 0.29 5.356E-22 cg24922143 chrl5 35014270 0.40 2.264E-22 cg09170903 chrl5 62457209 0.22 1.221E-14 cg25440893 chrl5 35091802 0.25 2.131E-22 cg25171685 chrl5 63334355 0.23 2.824E-14 cgl3181164 chrl5 37388828 0.21 4.339E-18 cg22097731 chrl5 63334436 0.33 1.563E-14 cgl3181974 chrl5 37389489 0.31 8.349E-19 cg25447873 chrl5 63548963 0.21 3.675E-20 cg01958086 chrl5 37389951 0.25 4.655E-18 cgl0916429 chrl5 64799784 0.24 1.129E-21 cg03951374 chrl5 37390176 0.23 3.169E-25 cgll479165 chrl5 65068594 0.25 1.166E-21 cgl3800209 chrl5 37390284 0.35 4.421E-19 cg21210224 chrl5 65186306 0.25 9.513E-16 cg07077665 chrl5 37395084 0.23 1.087E-16 cgl3702629 chrl5 66546648 0.23 3.764E-18 cg20305024 chrl5 40575730 0.20 4.921E-22 cg04805181 chrl5 66914759 0.23 9.252E-15 cgl2386646 chrl5 41787261 0.20 1.013E-15 cg09827761 chrl5 66947392 0.21 8.206E-15 cg27021986 chrl5 41805273 0.24 1.454E-17 cgl0402698 chrl5 67000045 0.22 5.585E-22 cg27496526 chrl5 41805530 0.29 3.274E-20 cg01678084 chrl5 67022087 0.26 5.683E-22 cg27494383 chrl5 41805868 0.32 5.275E-21 cgl9679123 chrl5 67430336 0.24 5.539E-23 cg03257179 chrl5 41805946 0.27 4.734E-22 cgl6670554 chrl5 68118985 0.24 6.971E-15 cg09206294 chrl5 42072687 0.22 9.229E-22 cg22459630 chrl5 68121028 0.24 1.05E-15 cg20066496 chrl5 43213993 0.20 2.31E-16 cg20557801 chrl5 68121177 0.25 2.179E-17 cg21245717 chrl5 43585934 0.27 5.481E-19 cg24880701 chrl5 68121563 0.24 6.025E-15

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cgl3989852 chrl5 68260324 0.22 8.652E-22 cg03698393 chrl5 89438795 0.27 5.104E-24 cg21890726 chrl5 68260574 0.25 7.762E-18 cg01647632 chrl5 89438905 0.24 5.18E-23 cg02613418 chrl5 68723914 0.28 4.067E-21 cg02071670 chrl5 89438918 0.27 1.572E-25 cgl4188232 chrl5 68724065 0.30 2.926E-18 cg03628719 chrl5 89438964 0.29 2.846E-26 cg04791080 chrl5 68771946 0.21 6.039E-23 cg26213453 chrl5 89455860 0.28 8.718E-22 cgl6068038 chrl5 69099678 0.21 7.868E-18 cg03951603 chrl5 89903565 0.25 9.625E-21 cg06022664 chrl5 69136313 0.23 2.491E-16 cg26662049 chrl5 89903672 0.25 1.714E-22 cg00017062 chrl5 70669548 0.27 3.736E-19 cg23934731 chrl5 89904873 0.24 1.266E-17 cg21511941 chrl5 72489609 0.29 5.259E-22 cg07627119 chrl5 89906172 0.21 8.363E-17 cg04098270 chrl5 72489686 0.33 1.026E-24 cg09683350 chrl5 89914466 0.21 1.213E-14 cg06776898 chrl5 73611079 0.21 9.353E-16 cg20738500 chrl5 89921156 0.21 1.478E-15 cg08450752 chrl5 73611451 0.33 3.201E-18 cg09969277 chrl5 89922328 0.25 2.084E-17 cg02453462 chrl5 73662002 0.22 9.019E-16 cg04164058 chrl5 89949694 0.20 4.202E-18 cgl6231923 chrl5 73923634 0.23 1.329E-23 cg22549870 chrl5 89949776 0.25 2.084E-18 cg00028013 chrl5 74218697 0.22 3.918E-20 cgl8724430 chrl5 89951787 0.24 1.515E-20 cg07317017 chrl5 74218715 0.21 2.437E-19 cgl3406145 chrl5 89952052 0.24 4.988E-20 cgl0372921 chrl5 74218733 0.22 6.01E-21 cgl4164044 chrl5 89952135 0.27 2.028E-21 cg04436755 chrl5 74218767 0.21 1.602E-22 cgl2254845 chrl5 89952272 0.25 7.037E-21 cg20652404 chrl5 74218904 0.22 1.268E-21 cg06622408 chrl5 89952299 0.21 8.575E-20 cg02916102 chrl5 74658244 0.29 3.191E-19 cgl8698788 chrl5 89952499 0.38 1.132E-19 cgl7588266 chrl5 74658330 0.31 6.631E-24 cg24738311 chrl5 89952632 0.25 1.341E-17 cgl6332610 chrl5 74658547 0.38 4.41E-22 cg26434983 chrl5 89952904 0.22 6.514E-19 cgl4855334 chrl5 74658553 0.29 4.238E-19 cg03457729 chrl5 89953295 0.27 1.881E-17 cg24578679 chrl5 74658573 0.28 8.048E-24 cg00766188 chrl5 89953370 0.20 3.511E-20 cg23727072 chrl5 75019087 0.23 4.077E-18 cg24653181 chrl5 90039582 0.29 7.287E-22 cg05549655 chrl5 75019143 0.22 6.79E-22 cgl8726691 chrl5 90039613 0.35 8.873E-22 cgl2101586 chrl5 75019203 0.21 5.024E-21 cg27507295 chrl5 90039794 0.26 5.101E-23 cg22549041 chrl5 75019251 0.27 4.369E-21 cg07485916 chrl5 90039805 0.27 1.931E-21 cg21523564 chrl5 75251491 0.49 1.5E-20 cgl0721782 chrl5 90039809 0.27 9.518E-21 cg05627522 chrl5 75251581 0.25 8.906E-22 cgll332236 chrl5 90039818 0.36 4.433E-18 cgl0680264 chrl5 75470927 0.22 9.191E-15 cg01837657 chrl5 90039822 0.41 9.698E-23 cg07044708 chrl5 75471034 0.20 2.976E-15 cgl0453365 chrl5 90039909 0.28 6.034E-22 cgl9642402 chrl5 77287762 0.22 9.144E-23 cgl2042113 chrl5 90039913 0.30 6.122E-22 cg26025891 chrl5 77287899 0.21 4.496E-26 cg09397246 chrl5 91427361 0.23 2.067E-21 cg06786153 chrl5 78327011 0.21 1.04E-24 cgll670789 chrl5 93208459 0.22 5.497E-16 cg02119938 chrl5 78505051 0.24 3.437E-20 cg08334034 chrl5 93615039 0.22 5.873E-21 cg27554782 chrl5 78933106 0.22 4.325E-24 cg21079003 chrl5 93615146 0.24 2.017E-20 cg09193347 chrl5 79381867 0.27 1.036E-19 cgl0959198 chrl5 93632896 0.26 7.264E-17 cg04947764 chrl5 79502127 0.22 3.15E-19 cgl8567924 chrl5 95870450 0.22 3.557E-16 cg25029264 chrl5 81426347 0.22 3.32E-14 cgl6086559 chrl5 96911531 0.21 1.048E-15 cgl4380111 chrl5 81426360 0.25 5.027E-17 cg26991025 chrl5 99091228 0.23 2.017E-19 cg24319381 chrl5 83316911 0.20 8.344E-17 cg01054354 chrl5 100272751 0.22 2.23E-15 cg07769790 chrl5 83317281 0.20 3.308E-19 cgl9350360 chrl5 100913948 0.26 4.415E-18 cgl6495212 chrl5 83317306 0.21 3.673E-18 cg25677261 chrl5 102009856 0.23 1.108E-21 cgl0398682 chrl5 83952019 0.21 1.886E-14 cg00659931 chrl5 102010125 0.21 2.19E-23 cgl8952647 chrl5 83953744 0.23 3.226E-16 cg09555736 chrl6 474271 0.21 1.933E-16 cgl4385245 chrl5 83953765 0.22 1.484E-16 cg05245533 chrl6 795877 0.23 2.704E-17 cg26429925 chrl5 83953775 0.22 1.547E-17 cg07970752 chrl6 817463 0.24 1.139E-14 cg22387369 chrl5 85360691 0.27 3.224E-15 cg05031521 chrl6 1030561 0.23 5.86E-18 cg03796321 chrl5 86162442 0.28 8.42E-22 cg09854626 chrl6 1030568 0.22 2.984E-15 cg04188862 chrl5 88801474 0.24 4.355E-20 cg08965276 chrl6 1030586 0.24 2.481E-15 cg04829853 chrl5 89438208 0.22 1.984E-16 cg08848958 chrl6 1384655 0.27 2.858E-18 cg02231729 chrl5 89438611 0.36 1.624E-18 cg05915293 chrl6 2041512 0.22 8.244E-17 cg08348496 chrl5 89438671 0.36 1.09E-19 cgl0286969 chrl6 2765843 0.29 4.525E-18 cg01367393 chrl5 89438731 0.24 8.392 E-25 cg05097643 chrl6 3018470 0.21 3.911E-16

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cg09674170 chrl6 3062382 0.22 1.374E-19 cg27267227 chrl6 29888023 0.21 1.105E-15 cg08199758 chrl6 3062426 0.23 8.376E-20 cg07300846 chrl6 29888571 0.21 3.762E-15 cg27009812 chrl6 3062597 0.21 3.343E-20 cg03696974 chrl6 29888670 0.23 1.441E-17 cg06117341 chrl6 3062653 0.28 4.522E-24 cg07160932 chrl6 29888733 0.21 2.268E-14 cg04715503 chrl6 3062795 0.25 7.009E-26 cg06985993 chrl6 30040055 0.22 1.418E-20 cg02732252 chrl6 3068014 0.24 6.59E-21 cgl6014085 chrl6 30406122 0.21 1.91E-25 cg08935125 chrl6 3068085 0.20 4.254E-15 cg26624796 chrl6 30406176 0.20 5.899E-20 cg22776856 chrl6 3072572 0.20 1.593E-21 cg03175771 chrl6 30661534 0.22 4.143E-18 cg07868599 chrl6 3079708 0.21 2.658E-19 cg06159340 chrl6 30907560 0.22 7.808E-19 cg27519622 chrl6 3079877 0.24 6.165E-23 cg27239280 chrl6 30907679 0.25 9.359E-18 cgl4134732 chrl6 3079894 0.24 1.959E-21 cgl7800442 chrl6 30908233 0.20 3.934E-17 cg07063883 chrl6 3079953 0.20 2.711E-21 cg08730348 chrl6 31214307 0.25 4.283E-23 cg02680314 chrl6 3097387 0.24 2.442E-21 cg05214748 chrl6 31214335 0.22 1.175E-23 cg07451886 chrl6 3097405 0.24 1.707E-22 cgl2100791 chrl6 31214417 0.28 9.514E-21 cg07891531 chrl6 3221328 0.23 7.124E-17 cg09115984 chrl6 31214426 0.26 3.769E-21 cg05048377 chrl6 3237964 0.26 2.51E-21 cg02900356 chrl6 31214494 0.25 3.89E-23 cg02970836 chrl6 3237991 0.33 9.23E-21 cg01059100 chrl6 31214607 0.27 1.168E-25 cg26988423 chrl6 3238423 0.20 8.192E-18 cg26770907 chrl6 48844808 0.20 1.125E-15 cg03281661 chrl6 3239458 0.23 1.03E-16 cg00083833 chrl6 50583273 0.29 1.395E-23 cgl2031863 chrl6 4587854 0.23 2.954E-16 cg04698114 chrl6 51184379 0.23 9.849E-16 cg09549813 chrl6 4587862 0.30 4.382E-19 cg00582524 chrl6 51184392 0.29 1.846E-16 cg09944213 chrl6 5037570 0.25 1.123E-18 cg09016242 chrl6 51185110 0.22 7.311E-16 cg04987053 chrl6 5038078 0.25 6.09E-16 cg06232807 chrl6 51185132 0.21 2.02E-16 cg00231389 chrl6 8806753 0.20 9.81E-17 cg01146232 chrl6 51185147 0.22 2.365E-15 cg00970396 chrl6 9107199 0.43 1.605E-22 cg01851378 chrl6 51186925 0.26 2.213E-18 cg03231735 chrl6 9184099 0.23 6.145E-20 cgl6501625 chrl6 54628759 0.24 6.439E-17 cg03309770 chrl6 10912478 0.21 4.677E-18 cgl6642791 chrl6 54966471 0.25 2.317E-16 cg26952618 chrl6 10912545 0.23 5.66E-19 cg01901262 chrl6 54966837 0.26 2.044E-17 cg09684846 chrl6 10912718 0.21 2.029E-15 cg09492451 chrl6 54967389 0.20 7.991E-17 cg09481483 chrl6 11734383 0.20 1.371E-22 cg02388378 chrl6 54968727 0.26 7.774E-19 cg08280468 chrl6 12997534 0.20 3.439E-18 cg01961105 chrl6 54968783 0.23 4.428E-20 cg03711016 chrl6 12997684 0.24 2.893E-14 cg07455757 chrl6 54968985 0.23 3.035E-20 cg03628000 chrl6 14596062 0.22 5.608E-23 cg06993307 chrl6 54969051 0.25 8.079E-22 cg09770579 chrl6 17407429 0.21 8.915E-23 cg27327911 chrl6 54969146 0.22 6.26E-19 cgl0087036 chrl6 19130461 0.24 1.467E-20 cg05317090 chrl6 54969706 0.29 1.779E-19 cg01028163 chrl6 19894948 0.21 1.833E-15 cg03782157 chrl6 54970302 0.23 2.194E-19 cg07519235 chrl6 19894978 0.43 3.034E-23 cg04786287 chrl6 54970523 0.21 4.265E-16 cg06088324 chrl6 19895321 0.29 8.774E-21 cgl2492345 chrl6 54971007 0.20 3.958E-20 cgl6596604 chrl6 21294947 0.37 1.351E-25 cg26470798 chrl6 54971598 0.21 1.867E-14 cg08214995 chrl6 22826243 0.26 2.028E-19 cg26053832 chrl6 54971600 0.21 7.689E-16 cg01932956 chrl6 22959525 0.26 4.404E-23 cgl2317456 chrl6 55512868 0.22 4.59E-17 cg03210314 chrl6 22959594 0.24 6.502E-20 cg01821058 chrl6 55512870 0.27 1.154E-17 cg00538458 chrl6 22959868 0.22 1.006E-16 cg09321400 chrl6 55690443 0.22 3.503E-18 cg22968966 chrl6 22959875 0.22 3.681E-18 cg01110759 chrl6 56672387 0.22 1.817E-15 cg03306374 chrl6 23847325 0.26 1.034E-14 cg09137696 chrl6 56672415 0.26 3.471E-16 cg03217795 chrl6 23847556 0.29 1.048E-20 cgl8438944 chrl6 56672525 0.26 4.111E-15 cg05436658 chrl6 23847568 0.22 1.029E-20 cg05486035 chrl6 56697088 0.32 5.243E-18 cg06505273 chrl6 24850292 0.22 6.185E-20 cg01544903 chrl6 56697229 0.32 3.564E-15 cg05037662 chrl6 25704296 0.23 5.2E-17 cgl7545418 chrl6 56709853 0.21 2.141E-15 cg23235241 chrl6 25704505 0.36 2.57E-25 cg27559661 chrl6 57125836 0.20 7.626E-16 cg03376794 chrl6 25704507 0.36 7.726E-25 cg26644853 chrl6 57406257 0.21 4.769E-21 cgl0292154 chrl6 27461445 0.33 3.577E-21 cg20427865 chrl6 57406353 0.25 7.996E-23 cg03662014 chrl6 29086271 0.26 1.658E-18 cg04452432 chrl6 57406511 0.21 1.073E-24 cg06453916 chrl6 29690524 0.22 5.345E-23 cg08096786 chrl6 57571099 0.30 6.235E-21 cg20065768 chrl6 29796685 0.21 8.682E-17 cg01616225 chrl6 57662347 0.25 2.365E-19

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cg03989617 chrl6 57662541 0.23 5.042E-21 cg09780231 chrl7 873452 0.24 5.375E-24 cg09109520 chrl6 57673258 0.28 8.736E-24 cgl8331855 chrl7 1131781 0.31 1.713E-22 cg07112337 chrl6 57917946 0.21 9.558E-15 cgll424456 chrl7 1131878 0.30 5.864E-18 cg08699646 chrl6 58019359 0.27 7.155E-17 cg26953640 chrl7 1174473 0.21 1.57E-14 cg00044665 chrl6 66400411 0.22 7.945E-23 cgll393185 chrl7 1202015 0.27 1.002E-16 cg09849405 chrl6 66612955 0.29 1.179E-16 cg04196298 chrl7 1480710 0.22 6.376E-20 cg01683883 chrl6 66613053 0.21 4.294E-18 cg25858132 chrl7 1808671 0.30 8.08E-21 cg08032924 chrl6 66613096 0.26 1.135E-19 cg02866639 chrl7 1808743 0.24 1.501E-20 cg04358214 chrl6 67143304 0.23 1.121E-14 cgl4769786 chrl7 1881333 0.29 4.29E-15 cg07816687 chrl6 67197186 0.25 8.568E-16 cgl7648080 chrl7 2141841 0.25 4.79E-20 cg09567485 chrl6 67203753 0.27 4.305E-19 cgl7119387 chrl7 2615431 0.21 1.969E-14 cg01005439 chrl6 67204010 0.31 5.245E-24 cg00668150 chrl7 2615720 0.23 2.088E-15 cgl3975336 chrl6 67204216 0.33 2.298E-25 cg04352272 chrl7 3289798 0.21 2.565E-15 cg06537680 chrl6 67204316 0.25 8.612 E-22 cg06468454 chrl7 3591377 0.24 6.047E-23 cg09974990 chrl6 67204447 0.32 3.599E-21 cg22280258 chrl7 4545157 0.20 1.853E-14 cg04890459 chrl6 67204681 0.26 4.173E-21 cg23350904 chrl7 4648580 0.23 1.406E-18 cg26783727 chrl6 67204807 0.20 1.081E-19 cg27453857 chrl7 4689640 0.23 6.724E-16 cg02909711 chrl6 67360805 0.24 4.27E-16 cgl4928057 chrl7 4891542 0.25 1.452E-24 cg05226168 chrl6 68118441 0.24 2.498E-22 cg27362525 chrl7 5019638 0.23 4.4E-16 cg00402172 chrl6 68118754 0.20 3.757E-21 cg01120173 chrl7 5019669 0.22 4.71E-14 cg09900242 chrl6 68676451 0.20 2.253E-15 cg05364567 chrl7 5019761 0.22 2.952E-16 cg07061260 chrl6 68676557 0.23 2.736E-16 cg08750459 chrl7 6558815 0.23 2.05E-16 cgl6562730 chrl6 71560187 0.24 3.784E-20 cg24451123 chrl7 6559656 0.23 1.824E-19 cg00840403 chrl6 71560205 0.23 8.656E-20 cg02374745 chrl7 6679564 0.24 1.243E-15 cg07201456 chrl6 75528813 0.24 1.359E-15 cg20723355 chrl7 6679597 0.23 3.644E-16 cg02501155 chrl6 79263473 0.23 2.216E-19 cg03760483 chrl7 6899297 0.23 9.264E-15 cg09422450 chrl6 79623618 0.27 7.922 E- 20 cg03404566 chrl7 6899310 0.25 2.274E-14 cg04317962 chrl6 79623625 0.30 1.48E-19 cg24173049 chrl7 6939795 0.25 2.449E-17 cg05000331 chrl6 79623678 0.24 5.388E-22 cg01019875 chrl7 6945620 0.25 9.21E-15 cgl6713262 chrl6 79623751 0.21 2.565E-15 cgll838224 chrl7 7287740 0.24 6.054E-17 cg03296797 chrl6 84870066 0.24 4.068E-21 cgl9056772 chrl7 7341616 0.26 6.735E-20 cg03476673 chrl6 84870203 0.23 4.323E-23 cg25563256 chrl7 7341641 0.22 3.996E-20 cg08844698 chrl6 85185607 0.24 3.178E-21 cgll731868 chrl7 7344050 0.21 2.567E-14 cg09556515 chrl6 85470485 0.22 2.128E-18 cg24479590 chrl7 7348322 0.23 1.259E-21 cg02124446 chrl6 85783537 0.20 1.787E-24 cg22637538 chrl7 7348327 0.20 3.286E-20 cg01250960 chrl6 85783863 0.26 1.148E-24 cg22237200 chrl7 7555298 0.25 5.4E-22 cg25714826 chrl6 85784062 0.29 2.766E-22 cg22761431 chrl7 7609416 0.25 1.11E-19 cg05463589 chrl6 88706426 0.23 5.287E-15 cgl0020356 chrl7 7906042 0.21 1.145E-17 cg03787864 chrl6 88717134 0.29 6.052E-19 cgl0708955 chrl7 8056950 0.26 1.05E-22 cg26537639 chrl6 88717374 0.34 3.078E-16 cg04658021 chrl7 8056967 0.22 5.151E-19 cg04879832 chrl6 88717456 0.35 7.906E-15 cg05562381 chrl7 8230350 0.27 6.644E-18 cg08843517 chrl6 88717464 0.31 8.674E-17 cg25498489 chrl7 8230483 0.27 7.669E-21 cg09025501 chrl6 88717472 0.30 2.194E-16 cgl5608939 chrl7 8907074 0.23 5.293E-18 cg03125427 chrl6 88717482 0.32 8.207E-17 cgl4615768 chrl7 8924093 0.20 1.881E-20 cg08177833 chrl6 88717537 0.30 4.357E-17 cgl5661389 chrl7 10018631 0.21 3.636E-14 cg00054525 chrl6 88717587 0.26 8.296E-16 cgl7278864 chrl7 12877321 0.27 4.338E-14 cgl0246531 chrl6 88717628 0.26 1.226E-19 cg08794157 chrl7 15164627 0.26 4.368E-21 cg24046411 chrl6 88717646 0.26 3.325E-19 cgll343211 chrl7 15686309 0.24 3.695E-17 cg05744675 chrl6 88717723 0.23 7.021E-20 cg08790676 chrl7 15686438 0.26 2.875E-17 cgl9790294 chrl6 88717755 0.28 6.234E-19 cgl6052975 chrl7 15821016 0.24 7.847E-23 cg26713109 chrl7 754463 0.20 6.787E-20 cg22758454 chrl7 16570483 0.26 2.712E-18 cgl8513062 chrl7 763049 0.26 1.57E-20 cgl3000649 chrl7 17626790 0.27 9.355E-24 cgl3417862 chrl7 855238 0.27 2.027E-22 cg00073010 chrl7 17627194 0.25 2.263E-19 cg07090980 chrl7 873255 0.21 1.642E-21 cg06488957 chrl7 17628152 0.25 2.245E-20 cg25293325 chrl7 873413 0.21 1.749E-22 cgl9447962 chrl7 17628656 0.28 5.382E-20

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cgl9439123 chrl7 17687621 0.22 2.814E-20 cg00672333 chrl7 36728456 0.27 7.904E-15 cg08358166 chrl7 18538271 0.24 1.786E-14 cgl0184983 chrl7 36734911 0.23 1.873E-14 cg07727884 chrl7 19290503 0.23 6.382E-24 cg20555674 chrl7 37321631 0.24 1.559E-16 cg25216196 chrl7 19290520 0.22 3.611E-25 cgl7154395 chrl7 37752605 0.22 2.846E-18 cgl0351914 chrl7 19290690 0.23 1.23E-22 cg00578638 chrl7 38334161 0.26 5.243E-18 cgl5119221 chrl7 19290755 0.25 1.848E-21 cgl4603620 chrl7 38334166 0.24 1.596E-17 cg20431135 chrl7 19290762 0.26 2.019E-21 cg25813864 chrl7 38334176 0.26 5.961E-17 cg06390079 chrl7 19648855 0.23 8.683E-19 cg03085312 chrl7 38465281 0.27 1.508E-26 cg24974737 chrl7 21367368 0.23 4.353E-21 cg08332908 chrl7 38465326 0.25 2.564E-24 cgl5922057 chrl7 25784714 0.20 8.749E-22 cg09858022 chrl7 38465333 0.25 4.566E-24 cgl3568106 chrl7 26835115 0.28 4.124E-20 cg22935450 chrl7 38465393 0.27 1.061E-24 cg21237418 chrl7 27045043 0.22 3.311E-20 cg03053374 chrl7 38465422 0.25 6.286E-23 cg03452174 chrl7 27045113 0.22 1.832E-21 cg00236832 chrl7 38465489 0.21 3.875E-25 cg22803868 chrl7 27045164 0.22 3.411E-21 cg26654286 chrl7 38465510 0.32 4.179E-24 cgl9982230 chrl7 27045302 0.22 2.815E-21 cg08580254 chrl7 38478807 0.26 2.15E-25 cg08217285 chrl7 27917879 0.23 1.257E-23 cgl3385210 chrl7 38599271 0.22 5.553E-17 cgl2080909 chrl7 27917982 0.31 1.624E-24 cgll961138 chrl7 38599366 0.25 2.579E-17 cg21468728 chrl7 27918207 0.22 5.729E-24 cgl7980404 chrl7 38601676 0.20 2.099E-18 cg20300175 chrl7 27918316 0.31 2.684E-21 cg03635766 chrl7 38607865 0.20 1.846E-22 cgl6755500 chrl7 27918338 0.35 3.124E-19 cgl0050661 chrl7 38821420 0.22 2.255E-14 cg00801512 chrl7 28996047 0.21 1.161E-20 cgll641791 chrl7 38821429 0.27 1.939E-14 cg07133749 chrl7 29249870 0.23 1.091E-17 cgll809014 chrl7 39067081 0.27 2.678E-23 cg26069230 chrl7 29250073 0.23 3.817E-20 cg05548912 chrl7 40464318 0.23 2.07E-18 cg00447970 chrl7 29719431 0.25 3.524E-20 cg06968912 chrl7 40573643 0.31 5.601E-25 cg02984614 chrl7 31618409 0.25 2.43E-16 cg00971050 chrl7 40573764 0.31 2.804E-23 cgl9942495 chrl7 32484027 0.23 3.604E-22 cg06654691 chrl7 40825980 0.25 4.614E-24 cg24613080 chrl7 32484035 0.29 8.666E-18 cg22806907 chrl7 40826212 0.21 9.675E-22 cgl9024969 chrl7 32905966 0.22 8.044E-17 cgl0162691 chrl7 41177409 0.36 1.382E-22 cgl4380270 chrl7 33700747 0.27 2.234E-17 cg05270634 chrl7 41177445 0.36 6.482E-22 cg01348733 chrl7 33700757 0.20 3.699E-16 cg04524477 chrl7 41363597 0.24 3.628E-18 cgl0911913 chrl7 33700817 0.24 1.696E-15 cg08377924 chrl7 41363628 0.24 8.031E-22 cgl8108623 chrl7 33701321 0.27 7.071E-20 cgl9548479 chrl7 41363737 0.37 2.933E-22 cg03668718 chrl7 33701350 0.23 3.864E-15 cg24940138 chrl7 41363741 0.39 3.008E-23 cgll309496 chrl7 33701353 0.22 1.189E-14 cg21211480 chrl7 41363774 0.36 2.655E-19 cg02927346 chrl7 34059260 0.24 2.244E-24 cgl5026277 chrl7 41363789 0.38 5.048E-23 cgl2700449 chrl7 34121837 0.21 8.516E-18 cg03049782 chrl7 41363891 0.29 8.476E-23 cg21150901 chrl7 34957586 0.22 7.295E-18 cg24008544 chrl7 41363899 0.34 4.097E-23 cg08967106 chrl7 35014412 0.23 4.001E-18 cgl8222083 chrl7 41364007 0.43 5.348E-21 cg00371418 chrl7 35014438 0.21 6.506E-16 cg22562494 chrl7 41607896 0.30 1.233E-22 cg23397741 chrl7 35014588 0.22 3.007E-17 cg22982093 chrl7 41669401 0.21 1.877E-21 cgl0547969 chrl7 35084975 0.23 4.79E-16 cgl0471976 chrl7 42386190 0.21 2.306E-22 cg08535474 chrl7 35149318 0.21 2.365E-16 cgl3102585 chrl7 42386208 0.25 5.858E-22 cg06679334 chrl7 35241844 0.27 7.925E-18 cg01635086 chrl7 42386326 0.32 1.42E-21 cgl6364121 chrl7 35291924 0.25 4.192E-17 cg03936721 chrl7 42386419 0.23 3.344E-22 cgl5001747 chrl7 35292587 0.21 3.08E-17 cg09691340 chrl7 42402882 0.38 5.784E-17 cgl0356613 chrl7 35294491 0.26 6.227E-16 cg25558103 chrl7 42835859 0.23 3.068E-18 cg05323725 chrl7 35294713 0.21 1.273E-16 cg08848774 chrl7 43047733 0.32 3.134E-15 cgl5291243 chrl7 35298199 0.25 1.446E-18 cg27395066 chrl7 43221220 0.32 4.511E-21 cgl4754787 chrl7 35299600 0.26 8.206E-17 cg00677574 chrl7 43221327 0.31 4.839E-22 cgl9760241 chrl7 35300010 0.20 2.539E-17 cg24180402 chrl7 43221464 0.32 2.703E-19 cg06105694 chrl7 36585340 0.26 8.742 E-26 cg06100756 chrl7 43221575 0.30 4.817E-24 cgl8960629 chrl7 36585452 0.31 2.176E-23 cg04945541 chrl7 43299826 0.24 3.702E-22 cg03930313 chrl7 36621405 0.22 1.356E-21 cg06421526 chrl7 43423130 0.21 7.808E-17 cg01514828 chrl7 36715074 0.27 9.003E-15 cgl5156975 chrl7 43449055 0.21 6.165E-19 cgl4862207 chrl7 36715798 0.23 1.306E-14 cg06452354 chrl7 43449123 0.24 4.743E-19

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cg04976685 chrl7 43449285 0.23 8.147E-22 cgl5417365 chrl7 56609082 0.25 1.302E-21 cg07778819 chrl7 43862927 0.26 8.625E-18 cg20370678 chrl7 58216297 0.32 3.05E-22 cg24394631 chrl7 43863000 0.23 3.376E-21 cg21158087 chrl7 58216415 0.24 6.214E-18 cgl8878992 chrl7 43974344 0.27 3.598E-14 cg21389753 chrl7 59480674 0.26 2.661E-18 cgl9156875 chrl7 43974446 0.36 9.21E-21 cg07095230 chrl7 59480730 0.21 6.935E-16 cg26606256 chrl7 43974804 0.22 1.366E-18 cg22675937 chrl7 59481571 0.22 2.789E-18 cgl4202850 chrl7 43974869 0.26 1.091E-21 cg26199241 chrl7 59529486 0.26 9.987E-20 cgll909912 chrl7 43974919 0.30 6.935E-21 cg02081266 chrl7 59529618 0.30 2.229E-18 cg04382470 chrl7 43974975 0.34 7.853E-23 cg26130488 chrl7 59530104 0.24 7.9E-19 cgl0224600 chrl7 43975063 0.31 8.372E-22 cg07265743 chrl7 59535253 0.20 3.276E-16 cgl7911788 chrl7 44343683 0.27 1.958E-20 cgl3213923 chrl7 60885491 0.25 3.175E-14 cg06093379 chrl7 44896080 0.22 1.43E-14 cg20752903 chrl7 60885671 0.22 8.851E-15 cgl6440629 chrl7 44896147 0.22 3.374E-16 cg22027897 chrl7 60885856 0.32 8.395E-17 cg00126034 chrl7 44896162 0.24 1.308E-16 cg09920557 chrl7 61553938 0.29 2.695E-16 cg06785746 chrl7 44896166 0.21 2.805E-18 cg25054907 chrl7 61553954 0.29 6.623E-18 cglll42826 chrl7 44896223 0.21 2E-14 cg02131967 chrl7 61554106 0.30 1.5E-14 cgl2379948 chrl7 44896424 0.26 3.885E-16 cg02822259 chrl7 61615504 0.32 1.207E-23 cgl5125338 chrl7 44899394 0.24 8.424E-21 cg22097768 chrl7 61615913 0.26 3.231E-18 cgl0024583 chrl7 45772800 0.27 4.062 E-23 cg04770088 chrl7 63225020 0.21 1.744E-18 cg03474202 chrl7 45855739 0.21 8.281E-21 cgl7415265 chrl7 63225111 0.23 9.159E-17 cg24803719 chrl7 45855879 0.23 2.717E-19 cg23493412 chrl7 63491688 0.24 8.358E-22 cg23391107 chrl7 45924227 0.24 3.495E-20 cg09980477 chrl7 66255444 0.20 2.189E-16 cg23008871 chrl7 45949743 0.28 2.468E-22 cg00059652 chrl7 67605498 0.21 2.972E-20 cg09065876 chrl7 45949756 0.28 1.405E-21 cgl2116288 chrl7 70215735 0.24 3.205E-20 cgl6913064 chrl7 45949878 0.22 5.057E-22 cg21000227 chrl7 70216183 0.24 1.935E-17 cg06395298 chrl7 46651225 0.20 6.306E-17 cg00482488 chrl7 70216332 0.31 1.704E-21 cg24938632 chrl7 46830125 0.22 2.61E-19 cg08195512 chrl7 71948430 0.26 7.107E-21 cgl3132370 chrl7 46830260 0.39 3.919E-24 cgl8156204 chrl7 71948613 0.32 4.82E-18 cg26736812 chrl7 48042353 0.21 2.603E-18 cgl3727849 chrl7 72210343 0.32 4.66E-25 cg24383056 chrl7 48071706 0.28 8.312E-17 cg21327194 chrl7 72443018 0.22 2.104E-23 cgl4672994 chrl7 48503057 0.24 7.259E-27 cg06594281 chrl7 73083692 0.21 2.565E-18 cg23674344 chrl7 48503163 0.30 2.888E-21 cg21306329 chrl7 73083876 0.25 4.503E-14 cg06520003 chrl7 48504157 0.22 9.973E-23 cg27619475 chrl7 73083881 0.25 4.809E-14 cg25792518 chrl7 48545950 0.22 1.392E-17 cgl7733616 chrl7 73083887 0.25 8.293E-15 cg06958829 chrl7 48546118 0.23 4.289E-21 cg04305621 chrl7 73084263 0.23 1.006E-24 cg22627841 chrl7 48546258 0.24 3.473E-15 cgl0829727 chrl7 73084309 0.22 1.499E-19 cgl9805005 chrl7 50234775 0.23 1.259E-14 cg09300114 chrl7 73084329 0.27 5.55E-21 cg01392772 chrl7 53342740 0.29 7.155E-18 cg25032094 chrl7 73583839 0.21 8.266E-19 cg05452524 chrl7 53343029 0.32 1.404E-20 cgl2184886 chrl7 73584029 0.22 7.689E-16 cgl5835232 chrl7 53343075 0.30 6.39E-22 cg06390536 chrl7 73584068 0.24 1.127E-17 cg02383154 chrl7 53343283 0.31 2.819E-24 cg22287064 chrl7 73584070 0.26 2.968E-17 cg01185682 chrl7 53343553 0.27 5.553E-17 cg03744440 chrl7 73584108 0.21 3.143E-15 cg01451391 chrl7 53343561 0.36 9.299E-20 cg08781140 chrl7 73584617 0.24 7.837E-16 cg24126768 chrl7 53645286 0.21 1.875E-16 cgl5043615 chrl7 74025708 0.20 1.475E-19 cgl9403377 chrl7 53800225 0.21 2.032E-16 cg22761670 chrl7 74268201 0.24 1.776E-20 cg08762247 chrl7 53800372 0.23 9.466E-19 cg02028751 chrl7 74378849 0.22 2.514E-16 cgl8040354 chrl7 53800484 0.30 4.832E-19 cg24757533 chrl7 74494286 0.20 2.33E-17 cg03233426 chrl7 53800554 0.20 2.673E-18 cgl3387113 chrl7 74696737 0.27 4.102E-22 cgl7178761 chrl7 55682851 0.22 2.848E-22 cgl5052447 chrl7 74696872 0.24 8.291E-23 cg00734904 chrl7 55888454 0.21 8.055E-24 cg01346013 chrl7 74836383 0.23 5.769E-20 cgl8347010 chrl7 55888532 0.32 1.481E-22 cg09777525 chrl7 74965708 0.33 6.217E-25 cg06817490 chrl7 55888548 0.34 1.685E-21 cgl2783819 chrl7 75369657 0.24 6.441E-17 cg08110785 chrl7 55952217 0.27 4.812E-19 cg02320862 chrl7 75370284 0.29 1.05E-19 cg05230392 chrl7 55976522 0.21 3.399E-20 cgl2985929 chrl7 75370611 0.23 3.166E-21 cgl2117658 chrl7 56406294 0.27 5.724E-18 cg00011616 chrl7 75672423 0.21 1.957E-16

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cgl9894975 chrl7 76355674 0.25 3.765E-15 cg04967578 chrl8 13641894 0.22 1.134E-16 cg07382998 chrl7 76880071 0.24 3.98E-19 cgl4179575 chrl8 13826399 -0.22 6.427E-17 cg06641285 chrl7 76921829 0.23 1.601E-19 cg02992546 chrl8 14748439 0.22 1.064E-16 cg05306745 chrl7 76921845 0.20 3.139E-17 cg05766064 chrl8 19262576 0.20 6.177E-19 cgl8749404 chrl7 76975944 0.24 1.197E-22 cg25890168 chrl8 19262819 0.24 4.823E-20 cg04927537 chrl7 76976091 0.20 1.355E-19 cg23267759 chrl8 19751335 0.32 2.935E-18 cg23225637 chrl7 76989965 -0.22 2.022E-14 cgl3421439 chrl8 21199515 0.24 1.299E-16 cg22687077 chrl7 76993374 -0.20 6.711E-18 cgl0096645 chrl8 24130851 0.26 6.729E-20 cg00902147 chrl7 76993394 -0.29 1.94E-19 cg26704078 chrl8 24131115 0.25 5.306E-23 cg04243822 chrl7 77030221 0.21 3.624E-20 cg06206801 chrl8 24131379 0.28 3.806E-25 cg26165269 chrl7 77765514 0.25 3.317E-14 cg06844968 chrl8 24131604 0.20 5.686E-23 cg00014830 chrl7 77765733 0.22 1.685E-17 cg05994094 chrl8 31020806 0.23 2.983E-16 cg04934382 chrl7 77766335 0.21 1.415E-17 cg20615848 chrl8 31020973 0.21 2.307E-15 cgl8733548 chrl7 77766817 0.23 1.18E-18 cgl3721404 chrl8 31739202 0.27 2.585E-14 cgl7280106 chrl7 77767084 0.22 3.505E-18 cgl3611347 chrl8 31739207 0.22 2.793E-18 cg03405260 chrl7 77786344 0.21 6.885E-21 cg08141495 chrl8 31739521 0.23 7.55E-17 cg06782090 chrl7 77787880 0.21 1.358E-17 cg22009464 chrl8 32173084 0.28 2.256E-19 cg22101190 chrl7 77896096 0.20 1.949E-17 cg26530706 chrl8 32173093 0.29 2.083E-18 cgl4193007 chrl7 77953016 -0.35 7.342E-20 cgl8420599 chrl8 32173206 0.25 6.441E-20 cg04194055 chrl7 77953088 -0.34 4.582E-21 cgl5610027 chrl8 32173227 0.27 3.498E-18 cg02386420 chrl7 78806870 0.29 6.609E-24 cg00628788 chrl8 33529997 0.26 1.848E-20 cgl8516619 chrl7 78806891 0.33 2.393E-23 cgl5142477 chrl8 43915662 0.23 1.046E-19 cg02080909 chrl7 79058333 -0.21 1.954E-15 cg08076830 chrl8 44774923 0.20 3.513E-18 cg00555905 chrl7 79140481 0.21 3.135E-17 cg06629130 chrl8 44787585 0.26 7.09E-19 cgl3710969 chrl7 79393463 0.23 7.269E-18 cg20026939 chrl8 44788898 0.24 3.815E-16 cg07016556 chrl7 79393532 0.21 3.14E-18 cg03744043 chrl8 45662275 0.22 9.141E-22 cg02447879 chrl7 79393682 0.26 1.217E-20 cgl4283454 chrl8 46449389 0.20 1.086E-16 cgll282657 chrl7 79615101 0.22 7.632E-17 cgl5677957 chrl8 47088780 0.20 5.583E-18 cgl8268547 chrl7 79615552 0.27 2.214E-20 cgl8866015 chrl8 49868552 0.21 1.209E-14 cgl6549644 chrl7 79652024 -0.21 7.57E-15 cg25767345 chrl8 54788969 0.25 2.221E-22 cgl5846886 chrl7 79790116 0.20 2.893E-18 cg20092531 chrl8 54789058 0.28 6.394E-16 cgl9563510 chrl7 79881483 0.22 1.395E-15 cg05826255 chrl8 55019307 0.22 4.549E-15 cgl8631330 chrl7 79899941 0.24 2.679E-17 cg22070406 chrl8 55019708 0.21 3.806E-17 cgl5866977 chrl7 79919578 0.29 1.669E-20 cg24811864 chrl8 55019711 0.23 1.278E-15 cgl9729649 chrl7 79919727 0.27 7.083E-22 cgl5222899 chrl8 55095249 0.28 1.287E-18 cgl8121066 chrl7 80794274 0.22 1.43E-14 cg25547580 chrl8 55103734 0.31 7.375E-17 cgl4621217 chrl7 80944134 0.31 8.726E-26 cg06067372 chrl8 55106337 0.20 1.052E-17 cg01780009 chrl7 80944193 0.20 4.944 E- 24 cg03636532 chrl8 55107236 0.21 1.041E-18 cg07483811 chrl8 2846237 0.21 1.925E-19 cg24771804 chrl8 55107755 0.22 1.059E-18 cgl5673034 chrl8 3499093 0.30 6.968E-19 cg00196827 chrl8 55108068 0.22 2.985E-15 cgl7298239 chrl8 3499253 0.29 1.819E-17 cg20956738 chrl8 55108537 0.28 6.026E-19 cg07352438 chrl8 5543548 0.20 2.312E-14 cgl0835584 chrl8 55108852 0.25 5.438E-18 cg06834637 chrl8 9017502 0.20 1.686E-19 cgl6941302 chrl8 55108947 0.22 4.598E-17 cgl8456459 chrl8 9707753 0.23 1.87E-18 cgl3518992 chrl8 55109119 0.24 7.246E-17 cgl7982102 chrl8 9707896 0.24 5.512E-19 cg03671802 chrl8 56941473 0.24 7.078E-19 cgl4595252 chrl8 9709061 0.23 4.751E-19 cg23085662 chrl8 59000860 0.20 4.62E-14 cg06825512 chrl8 10453969 0.23 1.32E-23 cgl9423014 chrl8 59560091 0.24 6.633E-20 cg03686593 chrl8 11149470 0.25 3.545E-14 cg06464594 chrl8 59560191 0.22 1.004E-20 cg20059140 chrl8 11751516 0.22 2.523E-22 cg01037637 chrl8 59560289 0.32 1.382E-18 cgll920122 chrl8 11751556 0.22 4.908E-24 cg03004714 chrl8 59560365 0.24 1.789E-18 cgl4612428 chrl8 11751566 0.23 5.267E-23 cg07980518 chrl8 59560394 0.31 2.959E-19 cg25594119 chrl8 11947571 0.31 9.088E-21 cg07486895 chrl8 59560433 0.29 4.092E-17 cgl4825976 chrl8 13611370 0.20 1.612E-15 cgl7020562 chrl8 59560495 0.25 8.398E-17 cg25374649 chrl8 13611400 0.23 4.364E-16 cg24213719 chrl8 60263646 0.22 3.404E-15 cg01022219 chrl8 13641735 0.23 4.714E-18 cg21602520 chrl8 60985380 0.21 8.747E-15

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cgl7602451 chrl8 60985645 0.21 6.063E-18 cgl9744936 chrl9 15343395 0.23 3.559E-16 cg24740531 chrl8 60985732 0.28 2.436E-17 cg26010734 chrl9 15344046 0.21 3.131E-16 cgl3644317 chrl8 70536461 0.29 2.589E-22 cgl8366919 chrl9 15344364 0.21 2.433E-18 cgl6171281 chrl8 73167422 0.25 3.07E-15 cg22522598 chrl9 15360953 0.21 1.126E-19 cgl7266581 chrl8 74799572 0.22 1.114E-16 cgl6695890 chrl9 15580310 0.22 1.433E-17 cg24027937 chrl9 709809 0.22 1.496E-21 cg22544863 chrl9 15580400 0.26 2.707E-19 cgOO 174901 chrl9 709889 0.21 7.246E-18 cgl8652900 chrl9 15580445 0.31 1.315E-17 cgl4796563 chrl9 1287576 0.20 3.647E-15 cgl8602913 chrl9 16022934 0.22 9.853E-18 cg22774088 chrl9 2253398 0.32 2.439E-21 cgl3618979 chrl9 16186840 0.24 5.591E-18 cgl8128164 chrl9 2253492 0.23 1.165E-23 cgll905624 chrl9 16186848 0.24 5.099E-16 cgl3735819 chrl9 2253850 0.26 7.773E-23 cg26968812 chrl9 16186873 0.21 2.709E-14 cg00330929 chrl9 2282010 0.28 1.247E-20 cgl5233183 chrl9 16187102 0.27 5.88E-15 cgl4337655 chrl9 2282207 0.21 4.765E-18 cg25593560 chrl9 16187364 0.27 4.876E-15 cg01559356 chrl9 2282568 0.24 4.349E-20 cg26149167 chrl9 16187889 0.30 7.076E-15 cg22294740 chrl9 2294961 0.22 6.541E-17 cg23715700 chrl9 16188274 0.24 9.565E-16 cgll231751 chrl9 2302783 0.22 4.677E-18 cg06590173 chrl9 16189360 0.22 6.538E-22 cg07498239 chrl9 2303032 0.27 3.199E-14 cg02381279 chrl9 16394366 0.23 2.08E-17 cg27280004 chrl9 2489065 0.31 7.729E-24 cg04324758 chrl9 16436671 0.24 1.624E-15 cgll859584 chrl9 3361374 0.22 3.114E-21 cg05906166 chrl9 16437057 0.22 3.564E-16 cgl5033068 chrl9 3801922 0.21 2.038E-18 cg08066035 chrl9 16999614 0.26 5.127E-18 cg08247397 chrl9 4607146 0.28 6.643E-17 cgl9006008 chrl9 16999768 0.22 1.656E-15 cg23698476 chrl9 4607318 0.21 7.836E-18 cgl8465484 chrl9 17138051 0.27 8.786E-17 cg01539133 chrl9 4607324 0.24 3.79E-17 cgl4923157 chrl9 17138063 0.25 8.464E-16 cgl6902746 chrl9 5338881 0.20 1.208E-20 cg24679890 chrl9 17246356 0.28 8.982E-21 cg02001390 chrl9 5338977 0.21 4.261E-21 cgll558551 chrl9 17516442 0.22 2.126E-21 cg24122124 chrl9 5339092 0.32 2.717E-19 cgl0357657 chrl9 17958633 0.21 2.249E-15 cgl6859884 chrl9 5829172 0.22 1.843E-16 cg05635754 chrl9 17958736 0.24 7.719E-16 cg07821354 chrl9 6768010 0.21 1.065E-14 cg07083818 chrl9 18385672 0.21 8.243E-18 cgl2024969 chrl9 6768022 0.21 2.339E-17 cgl7822706 chrl9 18415538 0.25 2.299E-21 cg02961707 chrl9 7927974 0.23 1.896E-16 cgl2026563 chrl9 18415804 0.21 1.212E-23 cg24470119 chrl9 8432416 0.25 7.476E-24 cg26624026 chrl9 18416001 0.20 1.099E-20 cg05890620 chrl9 10397612 0.23 3.875E-20 cg07561894 chrl9 18540208 0.22 8.395E-15 cgl4993276 chrl9 10397642 0.29 3.931E-22 cg20556517 chrl9 18540330 0.23 4.76E-14 cg04295144 chrl9 10407184 0.23 9.859E-15 cgl0740054 chrl9 18548004 0.21 5.273E-16 cg05614013 chrl9 11253754 0.21 7.059E-18 cgl3407975 chrl9 18705946 0.25 1.017E-15 cg07962303 chrl9 11253944 0.22 2.946E-17 cgl6673477 chrl9 18812017 0.21 1.604E-16 cg04328562 chrl9 11649701 0.21 1.465E-17 cgll609001 chrl9 18901843 0.21 2.371E-16 cgl0123421 chrl9 11785062 0.21 5.065E-19 cgl9485202 chrl9 18902081 0.23 2.594E-15 cgl0608596 chrl9 11785125 0.24 2.456E-18 cg02595575 chrl9 19221316 0.23 3.516E-17 cg27191312 chrl9 12750958 0.20 3.112E-14 cg01297721 chrl9 19373566 0.27 5.907E-16 cg24435924 chrl9 12978255 0.20 3.281E-18 cg22694191 chrl9 19373575 0.28 1.574E-17 cg08305551 chrl9 12978611 0.23 4.511E-17 cg25352836 chrl9 19625264 0.22 4.165E-16 cg02776664 chrl9 12978624 0.25 3.378E-17 cgl0784928 chrl9 19971578 0.21 2.252E-15 cg26870725 chrl9 12978805 0.31 3.267E-19 cg03317517 chrl9 20188803 0.26 1.596E-16 cgl6855845 chrl9 12991665 0.30 4.544E-18 cg05241461 chrl9 22816980 0.22 9.885E-15 cg00759699 chrl9 12991918 0.30 6.291E-17 cg00379720 chrl9 23185968 0.20 1.42E-14 cg00755063 chrl9 13275288 0.28 1.798E-20 cgl0836101 chrl9 30020886 0.21 2.878E-18 cgl7926950 chrl9 13983613 0.29 2.836E-22 cg25451303 chrl9 30720025 0.21 4.066E-16 cg06905453 chrl9 14089284 0.22 2.963E-17 cg01428589 chrl9 33167718 0.26 1.752E-15 cgl8642503 chrl9 14089711 0.21 1.326E-14 cg03070989 chrl9 34311482 0.25 3.79E-15 cg04752680 chrl9 14114100 0.20 2.569E-23 cgl8311360 chrl9 34311562 0.20 1.59E-18 cgl9267596 chrl9 15334821 0.27 2.741E-23 cg20439030 chrl9 34359847 0.21 1.511E-14 cg03562044 chrl9 15342749 0.23 4.336E-16 cg06882591 chrl9 34397628 0.23 7.208E-19 cg26477573 chrl9 15342915 0.26 1.058E-14 cg23200020 chrl9 35068555 0.35 1.161E-21 cgl7476026 chrl9 15343235 0.20 4.507E-16 cg07599133 chrl9 35068628 0.30 3.302E-24

cg04714041 chrl9 35068710 0.23 2.763E-16 cg22473620 chrl9 46379929 0.25 2.641E-23 cg26346108 chrl9 35329641 0.21 8.195E-20 cgl3546240 chrl9 46379991 0.33 6.258E-20 cg20229496 chrl9 35395800 0.23 3.024E-21 cgll716106 chrl9 46380134 0.36 4.844E-19 cgl7611193 chrl9 35395942 0.20 2.033E-19 cg23947326 chrl9 46504128 0.21 2.79E-15 cg26983177 chrl9 35395973 0.23 7.754E-25 cgl5229275 chrl9 46800054 0.26 2.266E-19 cg00515457 chrl9 35396203 0.24 5.83E-23 cgl9310908 chrl9 46800064 0.24 3.882E-24 cg06193578 chrl9 35396475 0.21 5.54E-20 cgl4117138 chrl9 46800085 0.46 9.218E-24 cg08543966 chrl9 35646150 0.23 4.302E-18 cgl0594090 chrl9 46800198 0.33 3.963E-24 cgl5426035 chrl9 36024685 0.24 4.128E-20 cgl4088357 chrl9 46800338 0.35 1.557E-21 cgl8435532 chrl9 36024802 0.20 1.342E-24 cg02879662 chrl9 46800467 0.29 2.84E-21 cgl7810176 chrl9 36035831 0.27 7.82E-15 cg09789590 chrl9 46800479 0.28 2.433E-23 cg21647257 chrl9 36523945 0.20 2.12E-18 cg05286653 chrl9 46800602 0.30 3.187E-24 cg22719241 chrl9 36524058 0.28 5.016E-20 cg27146050 chrl9 46801557 0.21 1.034E-17 cg24909548 chrl9 36736272 0.27 1.157E-14 cgl6672562 chrl9 46801672 0.29 3.447E-18 cg24096855 chrl9 38700334 0.23 6.892E-18 cg25987744 chrl9 46916588 0.27 1.591E-23 cgll631271 chrl9 38700487 0.25 6.637E-15 cgl8653451 chrl9 46917018 0.25 4.818E-22 cg27493151 chrl9 38701994 0.39 7.597E-18 cg03576469 chrl9 46917061 0.33 7.893E-23 cg09515953 chrl9 38747355 0.23 2.461E-17 cgl8709349 chrl9 46999274 0.21 1.272E-21 cg22557662 chrl9 38747374 0.27 3.158E-18 cg04689048 chrl9 46999289 0.22 5.427E-23 cg02571816 chrl9 38747378 0.26 3.523E-17 cg04255201 chrl9 46999307 0.21 6.782E-21 cgl4239515 chrl9 38885242 0.25 2.179E-16 cgl2098872 chrl9 47742726 0.29 5.866E-22 cgl2018098 chrl9 38885481 0.22 5.551E-17 cg22341310 chrl9 48048583 0.27 5.593E-20 cgl7759274 chrl9 39260954 0.29 8.093E-16 cg08602008 chrl9 48076841 0.21 1.329E-16 cg02711397 chrl9 39360313 0.21 3.825E-14 cg01532436 chrl9 48983942 0.32 3.178E-20 cg09474229 chrl9 39360330 0.23 6.238E-15 cg02590401 chrl9 48984071 0.28 1.676E-21 cg03231163 chrl9 39360465 0.27 4.786E-16 cg09371853 chrl9 48994877 0.20 4.004E-17 cg06244497 chrl9 39466575 0.27 2.135E-20 cg02804510 chrl9 49199965 0.22 1.444E-15 cgl4206172 chrl9 39466757 0.23 1.104E-20 cg08619932 chrl9 49200058 0.25 9.371E-16 cg00880452 chrl9 39694617 0.22 1.726E-18 cgl6867584 chrl9 49200180 0.23 3.268E-16 cg22290648 chrl9 39694709 0.24 1.321E-20 cg06339706 chrl9 49371285 0.22 7.878E-20 cg02863073 chrl9 39694831 0.26 4.794E-17 cg03039974 chrl9 49467169 0.20 1.238E-14 cg25509871 chrl9 40871557 0.21 6.001E-18 cg26522368 chrl9 49703932 -0.27 7.486E-20 cgl0274022 chrl9 40871697 0.24 6.148E-17 cgl8081863 chrl9 50015527 0.23 1.73E-19 cg08360726 chrl9 40871823 0.26 6.893E-17 cg09293816 chrl9 50015532 0.22 9.489E-20 cg07515422 chrl9 40993713 0.23 1.904E-16 cgl5528736 chrl9 50015780 0.24 6.644E-19 cg22498143 chrl9 40993991 0.32 6.798E-17 cg21604803 chrl9 50194662 0.25 1.973E-19 cg22030032 chrl9 41312792 0.21 7.039E-21 cgl0374084 chrl9 50666238 0.27 9.283E-16 cgl7435250 chrl9 41386441 0.24 5.122E-17 cg03344031 chrl9 50706387 0.24 9.765E-16 cg21111256 chrl9 41386507 0.28 8.818E-16 cg09281364 chrl9 50936093 0.20 1.322E-15 cg05372113 chrl9 41595975 0.31 1.182E-20 cgl8391955 chrl9 51303514 0.21 1.893E-17 cgl8591496 chrl9 41595977 0.28 3.496E-22 cgl9010054 chrl9 51416010 0.30 8.765E-21 cg07663732 chrl9 41882741 0.23 9.31E-22 cgl7355294 chrl9 51416098 0.26 1.375E-25 cg00498024 chrl9 41934170 0.20 2.39E-21 cg09953499 chrl9 51416202 0.36 1.302E-20 cgl6849024 chrl9 41934210 0.23 8.404E-23 cgl4283569 chrl9 51416213 0.32 3.078E-22 cg20557104 chrl9 41934313 0.26 4.412E-23 cg20115266 chrl9 51416517 0.23 6.572E-20 cg00513941 chrl9 42437245 0.22 1.006E-14 cg24512400 chrl9 51522561 0.31 7.757E-17 cg04319276 chrl9 42445244 0.20 8.571E-16 cgl5910208 chrl9 51522588 0.27 3.917E-17 cgll584690 chrl9 42574196 0.26 2.683E-21 cg04772683 chrl9 51522641 0.30 9.91E-15 cgl8397073 chrl9 42600278 0.21 1.266E-15 cgl8437710 chrl9 51522894 0.32 3.391E-26 cgl6517523 chrl9 42927074 0.26 5.762E-19 cgl8781966 chrl9 51523159 0.21 3.858E-22 cg24276035 chrl9 42927286 0.24 4.822E-16 cgl8542056 chrl9 51523205 0.27 3.228E-23 cg07517893 chrl9 45889164 0.31 9.847E-16 cg03307401 chrl9 51568260 0.29 1.228E-14 cg08243728 chrl9 45905890 0.33 5.936E-23 cg20104456 chrl9 51568523 0.33 6.529E-21 cgl2542255 chrl9 45976195 0.21 2.152E-15 cg22689630 chrl9 51568918 0.21 1.597E-17 cg21570209 chrl9 46367987 0.21 2.506E-16 cgl8563413 chrl9 51843854 0.29 3.574E-18

_

cg25417766 chrl9 52191468 0.23 1.3E-15 cg03002352 chr2 17699688 0.30 1.264E-21 cg08065657 chrl9 52223099 0.23 3.741E-20 cg21642176 chr2 17699740 0.24 3.685E-17 cg06878361 chrl9 52390810 0.22 4.936E-16 cg04804377 chr2 17699746 0.25 2.646E-15 cg03562414 chrl9 52391078 0.24 9.441E-16 cgl0167837 chr2 17699762 0.26 4.899E-17 cgl0635122 chrl9 52391090 0.25 7.925E-16 cg25565383 chr2 17699773 0.24 2.479E-16 cg24794228 chrl9 52391166 0.27 3.407E-16 cgl5124757 chr2 17699904 0.28 2.914E-19 cgl0783469 chrl9 52391234 0.25 1.577E-17 cg26631984 chr2 17719375 0.20 1.855E-20 cgl6731240 chrl9 52391250 0.29 2.346E-18 cg07098902 chr2 17720407 0.20 1.035E-14 cg23010048 chrl9 52391257 0.27 4.175E-17 cgll509669 chr2 17720758 0.21 1.49E-15 cgll269599 chrl9 52391304 0.26 1.523E-17 cgl4482308 chr2 18059109 0.28 4.965E-19 cg09547119 chrl9 52391367 0.25 5.496E-15 cg27365825 chr2 18059130 0.27 1.314E-17 cgl2227172 chrl9 52391411 0.25 6.482E-16 cg06530338 chr2 19561612 0.23 9.057E-18 cg21549195 chrl9 52452368 0.25 6.667E-15 cgl5339720 chr2 20425649 0.21 1.922E-23 cg24886257 chrl9 52452447 0.29 1.268E-17 cg25608973 chr2 21022431 0.23 2.245E-14 cg22455450 chrl9 53038972 0.32 3.877E-22 cg01203385 chr2 21022844 0.21 5.71E-15 cg20618441 chrl9 53039444 0.26 2.343E-17 cgl4903097 chr2 21023042 0.26 4.858E-14 cg09418984 chrl9 54369447 0.20 1.165E-14 cg03445151 chr2 23516881 0.26 1.343E-20 cg09503045 chrl9 55592453 0.20 1.256E-18 cgl9735698 chr2 23729523 0.21 5.141E-21 cg21121496 chrl9 55592930 0.23 3.156E-22 cgl4067761 chr2 23840739 0.20 1.818E-16 cgl2020396 chrl9 55593580 0.27 1.156E-15 cg01853276 chr2 24162441 0.22 4.017E-15 cg22372930 chrl9 55630001 0.21 1.829E-18 cg22480783 chr2 25149622 0.25 8.829E-19 cgl6890428 chrl9 55866412 0.21 4.408E-17 cg01884057 chr2 25150051 0.22 4.209E-21 cg03735012 chrl9 55964092 0.27 1.743E-14 cg20172627 chr2 25439110 0.21 2.476E-16 cgl5229747 chrl9 56097663 0.23 4.205E-19 cgl0648670 chr2 25439375 0.28 1.807E-21 cg03142586 chrl9 58220080 0.25 1.979E-22 cgll354105 chr2 25475805 0.21 6.099E-21 cgll294513 chrl9 58220295 0.30 8.595E-21 cg23780110 chr2 26045244 0.21 4.387E-19 cg05661282 chrl9 58220370 0.37 1.452E-20 cg22898783 chr2 26204699 0.22 9.486E-22 cg21790626 chrl9 58220494 0.32 4.168E-23 cg24563094 chr2 26395458 0.24 2.543E-15 cg27049766 chrl9 58220516 0.32 6.235E-21 cgll691298 chr2 26396787 0.24 2.507E-17 cg03234186 chrl9 58220657 0.28 5.732E-22 cg08781325 chr2 26521777 0.21 6.667E-21 cg08668790 chrl9 58220662 0.30 1.39E-21 cgll525280 chr2 26624667 0.20 8.086E-15 cgl2506930 chrl9 58220718 0.30 2.33E-21 cgl3414212 chr2 26624823 0.22 3.212E-15 cg26465391 chrl9 58220773 0.24 3.695E-22 cg04726446 chr2 26624865 0.21 2.769E-14 cg01268824 chrl9 58220818 0.29 1.775E-20 cgl4273450 chr2 26624934 0.30 1.337E-16 cg27324426 chrl9 58220837 0.26 5.664E-20 cg08789022 chr2 27484942 0.24 6.005E-18 cgl9416570 chrl9 58715677 0.23 5.889E-21 cg05901357 chr2 27529325 0.20 4.13E-20 cg26698460 chrl9 58716004 0.23 2.871E-22 cgl7689799 chr2 27529540 0.26 1.992E-17 cg22720790 chrl9 58716032 0.23 1.201E-20 cg20842253 chr2 27529788 0.34 2.088E-16 cgl5237857 chr2 45511 0.20 1.201E-20 cg01985390 chr2 27529981 0.26 1.613E-20 cg07065111 chr2 5831213 0.26 1.426E-17 cg06536868 chr2 27530884 0.23 3.911E-16 cg20927661 chr2 5837002 0.22 1.932E-16 cg23107161 chr2 27938371 0.20 2.643E-15 cg00078318 chr2 5837429 0.24 5.074E-19 cg01020696 chr2 27958142 0.22 7.062E-16 cgl4820415 chr2 6121680 0.25 7.471E-18 cg06744545 chr2 27958421 0.29 8.795E-16 cgl3217590 chr2 6122107 0.22 6.615E-19 cg00510539 chr2 27958611 0.28 6.575E-15 cgl8091469 chr2 8724060 0.28 2.362E-14 cgl5129506 chr2 27958712 0.27 6.096E-20 cg03959186 chr2 9893528 0.25 3.884E-22 cg05613116 chr2 27958722 0.29 2.126E-18 cg20648229 chr2 10111071 0.21 7.638E-20 cgll906781 chr2 28183394 0.26 6.471E-22 cg25433316 chr2 10197543 0.27 4.609E-19 cg01777397 chr2 29337946 0.24 5.017E-17 cgll385684 chr2 12858604 0.24 2.968E-15 cg07285673 chr2 29337984 0.25 4.37E-17 cg04699104 chr2 12858912 0.42 2.35E-16 cg09695033 chr2 29337988 0.27 4.025E-18 cgl3221363 chr2 12859103 0.30 1.054E-23 cg06333058 chr2 29338077 0.30 2.863E-15 cg05360477 chr2 12959313 0.22 3.065E-19 cg25737323 chr2 29338100 0.37 3.589E-16 cg08134504 chr2 16245936 0.21 2.283E-22 cgl3257636 chr2 29338109 0.33 9.253E-15 cg04163638 chr2 16832247 0.21 3.387E-21 cg23428985 chr2 29338113 0.36 5.449E-15 cg26119367 chr2 17699620 0.29 2.119E-20 cg23255835 chr2 29338121 0.35 2.29E-15

_

cg20495819 chr2 30448529 0.23 1.153E-17 cg20623601 chr2 46526843 0.21 3.276E-15 cg07902749 chr2 37813553 0.28 2.974E-23 cg25124739 chr2 46527098 0.23 2.602E-17 cg06522768 chr2 38265635 0.22 5.7E-20 cgl4141458 chr2 46770817 0.27 1.412E-19 cg06202585 chr2 38325802 0.20 1.295E-18 cg03531247 chr2 50573485 0.21 2.307E-16 cg02886589 chr2 39892450 0.24 3.819E-22 cgl4875171 chr2 50574196 0.20 3.411E-16 cgl8968196 chr2 39892502 0.25 1.448E-18 cgl7677030 chr2 50575069 0.24 4.387E-16 cgl0708761 chr2 39892612 0.20 6.508E-16 cgl3906811 chr2 50575093 0.22 1.308E-21 cgl4411266 chr2 40679582 0.20 4.291E-17 cg07529754 chr2 50575098 0.22 8.49E-17 cgl7892159 chr2 42274610 0.26 2.374E-20 cgl9664945 chr2 54087343 0.20 6.032E-19 cg24631482 chr2 42329446 0.22 7.37E-15 cg20786074 chr2 56150255 0.30 5.81E-25 cg23561979 chr2 42329535 0.25 2.091E-15 cg03122624 chr2 56150341 0.27 7.301E-26 cg20289949 chr2 43019614 0.25 3.008 E- 14 cgl6100120 chr2 56150475 0.26 1.139E-24 cg26360792 chr2 43019997 0.25 6.18E-15 cg05385513 chr2 56150478 0.27 1.75E-25 cg27299406 chr2 43020013 0.27 5.296E-15 cg06192497 chr2 63276216 0.23 IE-14 cg09480054 chr2 43020129 0.25 1.066E-16 cg27364741 chr2 63281069 0.20 1.155E-15 cg01561916 chr2 43020169 0.29 4.575E-17 cg04654530 chr2 63282702 0.22 1.636E-15 cgl7246140 chr2 43020264 0.27 2.798E-18 cg07974511 chr2 63283013 0.24 4.35E-14 cg05986933 chr2 43020457 0.28 1.407E-19 cg21472506 chr2 63283967 0.27 2.366E-16 cgl5850851 chr2 43446987 0.21 2.946E-15 cg23229261 chr2 63284066 0.21 2.122E-14 cg08750440 chr2 43447375 0.24 3.021E-15 cgl0122865 chr2 63284132 0.24 1.482E-15 cg09983326 chr2 43451308 0.22 1.551E-14 cg25371919 chr2 63284481 0.22 9.371E-16 cg24304789 chr2 43451423 0.25 2.036E-14 cgl9763461 chr2 63284557 0.26 7.589E-18 cg23288298 chr2 43451559 0.24 4.574E-15 cg05092308 chr2 63285365 0.21 4.706E-18 cgl8856652 chr2 43864913 0.30 2.112E-23 cgl8947951 chr2 63285739 0.26 1.823E-18 cgl5523958 chr2 43864929 0.26 2.971E-23 cg27315333 chr2 63285950 0.21 1.945E-16 cgl5754153 chr2 43865055 0.25 4.438E-20 cgll536474 chr2 63286049 0.32 7.482E-17 cg09760908 chr2 45028712 0.22 4.932E-17 cg25168494 chr2 63286355 0.24 9.416E-21 cg00028211 chr2 45028802 0.20 8.604E-18 cgl0927449 chr2 63286621 0.22 1.729E-21 cg20536041 chr2 45029004 0.26 1.958E-20 cgl0017626 chr2 65085243 0.21 4.178E-21 cgl9893751 chr2 45029285 0.22 7.211E-16 cgl7459215 chr2 66298242 0.22 7.444E-18 cgl9025113 chr2 45155201 0.26 3.604 E- 20 cgl9572637 chr2 66660175 0.23 3.051E-18 cgl8969232 chr2 45156937 0.22 5.938E-18 cg25721451 chr2 66662764 0.22 6.245E-17 cg22884656 chr2 45157296 0.26 4.035E-17 cg01406988 chr2 66662810 0.25 6.623E-19 cg23325963 chr2 45160093 0.27 3.484E-17 cg06796713 chr2 66664871 0.20 5.54E-16 cg24981593 chr2 45160253 0.24 1.039E-18 cg23398076 chr2 66664960 0.24 9.12E-18 cg03714619 chr2 45160445 0.31 2.177E-18 cg00995986 chr2 66665428 0.22 6.847E-18 cg02155398 chr2 45160490 0.21 1.519E-16 cg23972738 chr2 66667039 0.24 1.704E-15 cgll218954 chr2 45164864 0.24 9.096E-17 cgl2055515 chr2 66735203 0.21 1.092E-21 cgl5393275 chr2 45165193 0.20 5.899E-17 cg21581504 chr2 68545960 0.20 9.754E-17 cg06622151 chr2 45168246 0.22 2.711E-16 cg22400703 chr2 68545995 0.23 1.446E-16 cg23808946 chr2 45169548 0.28 2.444 E- 15 cg06275642 chr2 68546038 0.21 7.51E-18 cg02147764 chr2 45169681 0.24 2.359E-18 cg06635952 chr2 70025869 0.25 2.97E-24 cg02649597 chr2 45171621 0.24 4.663E-20 cg09175843 chr2 70313417 0.26 4.159E-14 cg00097146 chr2 45171818 0.33 6.631E-18 cgl0954469 chr2 71115370 0.27 2.821E-14 cg08696165 chr2 45172169 0.26 2.333E-18 cg22876812 chr2 71116188 0.32 1.518E-20 cgl9756790 chr2 45176863 0.29 1.903E-19 cgl0617784 chr2 71134586 0.27 7.955E-19 cg26855801 chr2 45176983 0.30 1.716E-18 cgl7649293 chr2 71134791 0.21 5.16E-17 cgl3704086 chr2 45177125 0.23 5.363E-15 cg20814026 chr2 71205520 0.24 3.067E-20 cg24673771 chr2 45180267 0.21 4.768E-15 cg05492660 chr2 71205564 0.22 6.312E-16 cg21875802 chr2 45231382 0.21 1.506E-16 cg23060872 chr2 71205685 0.22 2.055E-17 cg02711647 chr2 45237689 0.32 1.594E-16 cgl8006568 chr2 71205891 0.27 3.935E-21 cgl8623980 chr2 45240563 0.23 2.821E-17 cgl5165122 chr2 71206291 0.26 1.359E-18 cg07835844 chr2 45879684 0.21 7.91E-18 cgl2245706 chr2 71823484 0.21 1.677E-18 cgll505026 chr2 46067299 0.20 1.577E-19 cgl4196395 chr2 71823517 0.20 9.874E-17 cg24046888 chr2 46526785 0.24 1.654E-14 cg24516106 chr2 72079413 0.23 3.942E-19

cg25705148 chr2 72079498 0.20 9.638E-19 cg02648057 chr2 102867466 0.22 2.93E-15 cgl6928066 chr2 73147814 0.23 1.926E-19 cg08189989 chr2 105459164 0.22 2.45E-14 cgl4702570 chr2 74259524 0.23 1.759E-18 cgl9513834 chr2 105470561 0.22 1.079E-15 cg05890377 chr2 74357713 0.27 1.887E-14 cgl7912835 chr2 105478804 0.21 3.788E-19 cg04542030 chr2 74375469 0.27 2.885E-25 cg25305879 chr2 106814630 0.22 3.884E-23 cg02051239 chr2 74375507 0.28 4.963E-21 cg26001902 chr2 108602979 0.25 3.272E-17 cg08864042 chr2 74607470 0.23 5.806E-20 cgl6232126 chr2 108603005 0.24 7.183E-19 cg20303028 chr2 74607507 0.25 1.865E-20 cgl6528895 chr2 108994311 0.24 8.001E-16 cgl4601444 chr2 74607536 0.22 1.937E-21 cg23986590 chr2 109934728 0.21 3.637E-22 cg05413277 chr2 74642087 0.20 3.244E-20 cg20157753 chr2 113594343 0.21 5.7E-18 cgl3888593 chr2 74642470 0.21 1.427E-18 cg07935264 chr2 113594375 0.22 2.71E-19 cg04255230 chr2 74727010 0.22 2.233E-19 cg26230651 chr2 114048973 0.21 6.265E-19 cgl8409528 chr2 74741136 0.22 4.799E-16 cgl2666279 chr2 115918745 0.22 1.834E-15 cg07990546 chr2 74742309 0.22 4.528E-14 cg04075191 chr2 115919785 0.22 1.474E-17 cg26117023 chr2 74782096 0.24 1.061E-14 cg01718116 chr2 115919829 0.21 7.842E-16 cg02109484 chr2 74875253 0.20 5.091E-15 cg23729417 chr2 118593926 0.24 1.937E-20 cg02611848 chr2 74875387 0.23 7.698E-16 cg08838158 chr2 118594167 0.24 1.482E-21 cgl7349389 chr2 80530770 0.23 1.369E-16 cg21858380 chr2 119916486 0.22 1.149E-17 cg07475885 chr2 85107320 0.32 8.34E-20 cg23689428 chr2 121223964 0.24 4.327E-21 cg03604892 chr2 85107447 0.23 3.947E-19 cg25334934 chr2 121269348 0.23 1.767E-18 cg20653012 chr2 85107488 0.27 6.992E-20 cg27114644 chr2 121344729 0.21 6.831E-22 cg05621339 chr2 85483362 0.21 1.021E-20 cg25756780 chr2 121345047 0.26 3.146E-22 cg09337254 chr2 85640762 0.34 8.669E-28 cgl3283952 chr2 121412005 0.24 1.936E-16 cgl6437908 chr2 85640810 0.37 5.307E-23 cg04864807 chr2 121412139 0.26 8.474E-19 cg02242344 chr2 85640943 0.33 2.868E-27 cg08062049 chr2 121427380 0.32 1.719E-22 cg21654383 chr2 85641076 0.24 1.44E-18 cg21791662 chr2 121625208 0.20 2.79E-20 cg07245678 chr2 85641254 0.22 6.378E-18 cg03287111 chr2 121625634 0.22 1.173E-16 cgl9513321 chr2 85811432 0.24 2.056E-18 cgl2366772 chr2 122041891 0.21 6.878E-20 cgl3803976 chr2 87016129 0.24 4.006E-23 cgl4557510 chr2 122042345 0.27 6.445E-19 cg26057751 chr2 87016259 0.26 1.275E-20 cg04175027 chr2 123418722 0.27 4.149E-27 cg07152196 chr2 87016436 0.25 1.815E-22 cgl7080163 chr2 123418757 0.30 9.293E-24 cgl2691004 chr2 88352949 0.21 9.228E-21 cg04178787 chr2 123418787 0.32 5.632E-25 cgl3491584 chr2 88752836 0.20 5.967E-16 cgl5750501 chr2 123419027 0.20 1.996E-26 cg22762844 chr2 95692424 0.20 1.033E-15 cgl4657277 chr2 123419093 0.23 1.482E-23 cgl9762657 chr2 95692524 0.21 3.622E-18 cgl3358636 chr2 124782263 0.21 4.925E-15 cg07779387 chr2 95873465 0.22 7.777E-20 cg22830113 chr2 127783168 0.26 9.199E-18 cg24161793 chr2 96990762 0.23 2.736E-22 cgl4706852 chr2 127976351 0.25 1.193E-26 cg06909469 chr2 96990800 0.22 9.016E-21 cgl7032602 chr2 129076392 0.24 1.046E-20 cgl7932631 chr2 96990861 0.21 3.364E-25 cg03064940 chr2 129320987 0.22 6.467E-21 cg05497345 chr2 96990914 0.29 1.503E-21 cg08566455 chr2 130971164 0.30 6.176E-19 cgl3997864 chr2 96990982 0.23 1.429E-20 cgl0204868 chr2 131512971 0.24 1.656E-18 cg08983217 chr2 96991149 0.21 2.345E-22 cg01179012 chr2 131595107 0.22 1.169E-16 cgl9515245 chr2 97151922 0.22 8.416E-18 cg03750144 chr2 131595152 0.28 1.474E-18 cg22352818 chr2 97193289 0.29 4.112E-24 cg08901662 chr2 131595321 0.44 1.554E-20 cg26051755 chr2 97198107 0.20 8.501E-23 cg05885936 chr2 132088912 0.33 9.973E-24 cgl4174055 chr2 97203640 0.21 4.789E-20 cg21901277 chr2 132152297 0.25 8.51E-19 cgl9954537 chr2 97204401 0.24 1.177E-14 cg08613144 chr2 133428836 0.23 1.753E-18 cg08883078 chr2 97291520 0.26 8.172E-21 cg00113096 chr2 134119805 0.29 4.121E-25 cg20312012 chr2 97331035 0.23 1.803E-20 cg00697992 chr2 139537131 0.28 1.963E-22 cgl9370054 chr2 98964186 0.24 2.562E-16 cg02081701 chr2 139537197 0.35 5.818E-20 cg21488538 chr2 98964436 0.23 9.277E-15 cgl6405026 chr2 145281942 0.23 9.963E-17 cgl9043574 chr2 99439533 0.33 8.753E-18 cgl9053239 chr2 149645394 0.29 8.382E-19 cgl7968795 chr2 99553406 0.27 8.467E-21 cgl0664112 chr2 149645559 0.25 6.518E-18 cg04787024 chr2 99553442 0.36 2.105E-18 cgl0824705 chr2 149645724 0.29 1.294E-21 cg09236434 chr2 99553642 0.25 1.27E-17 cg06118384 chr2 149645798 0.23 5.782E-20

cg00760729 chr2 161236088 0.22 2.484E-17 cg25652029 chr2 182321786 0.21 6.991E-17 cg00314029 chr2 161348665 0.23 1.658E-20 cgll947981 chr2 182322749 0.25 1.801E-16 cg02772995 chr2 161348781 0.23 1.365E-16 cgl6640855 chr2 182543233 0.25 6.969E-18 cgl9914919 chr2 161992878 0.24 1.192E-22 cg04299439 chr2 182547599 0.22 1.037E-19 cg21211367 chr2 162094118 0.20 2.038E-17 cg01481989 chr2 183731169 0.22 2.892E-16 cg26210445 chr2 162273326 0.30 5.084E-18 cg00184203 chr2 187558402 0.20 6.272E-24 cg22794704 chr2 162273437 0.27 1.501E-16 cg23477967 chr2 188419087 0.34 2.131E-21 cgl4416523 chr2 162273928 0.20 1.513E-16 cg06855337 chr2 189489191 0.23 1.167E-22 cg23161999 chr2 162283189 0.28 7.907E-22 cg23502162 chr2 189839015 0.24 1.397E-19 cg01419831 chr2 162283705 0.21 8.154E-21 cgl8544564 chr2 189839120 0.24 6.779E-25 cg27404023 chr2 162283994 0.24 8.964E-20 cg20770175 chr2 189839474 0.21 1.558E-22 cgl6653620 chr2 162284135 0.28 1.084E-21 cg09211763 chr2 190044504 0.24 5.212E-20 cg22677715 chr2 162284644 0.22 5.261E-21 cg07875385 chr2 190044601 0.22 6.384E-20 cgl4781189 chr2 163695111 0.21 5.187E-17 cg22774472 chr2 190044636 0.21 5.356E-21 cgl9402991 chr2 164204915 0.22 2.37E-14 cgl0765212 chr2 190044638 0.23 2.808E-22 cg06372850 chr2 164205188 0.22 1.161E-19 cg01385959 chr2 190119363 0.22 7.85E-22 cg04319873 chr2 164205343 0.23 1.72E-20 cgl0168635 chr2 191044980 0.25 3.42E-25 cg03467825 chr2 171551893 0.21 2.241E-21 cgll448068 chr2 191045026 0.31 8.622E-23 cg04522045 chr2 172958324 0.21 5.652E-20 cg08350814 chr2 191045309 0.34 8.792E-17 cgl6573755 chr2 172958337 0.20 2.119E-19 cg06532037 chr2 191045430 0.28 1.341E-15 cg06040206 chr2 172961280 0.28 3.83E-18 cgl4210694 chr2 191045632 0.23 7.422E-19 cg02728483 chr2 172965081 0.23 2.306E-18 cgll097717 chr2 191045635 0.24 5.418E-19 cg07687548 chr2 172965280 0.23 5.525E-16 cgl5313226 chr2 191045668 0.27 3.028E-18 cg20935165 chr2 172972840 0.23 1.039E-17 cgl9906093 chr2 191045697 0.24 6.028E-19 cg00488692 chr2 174877566 0.24 3.045E-15 cg22003435 chr2 191045885 0.25 3.72E-23 cg24522254 chr2 174878113 0.23 1.603E-23 cg26187876 chr2 191514902 0.25 8.896E-17 cg05298922 chr2 175191045 0.27 2.055E-14 cg26191447 chr2 191656418 0.23 1.331E-20 cgl9049194 chr2 175193754 0.21 7.851E-18 cgll508595 chr2 192135315 0.24 1.761E-22 cg20345562 chr2 175197892 0.22 1.25E-16 cg08390172 chr2 192711905 0.23 1.358E-15 cg00178897 chr2 175208588 0.20 2.292E-15 cgl9376851 chr2 200334137 0.21 1.418E-15 cg01356950 chr2 175546714 0.22 4.58E-19 cgl3283765 chr2 200853063 0.29 2.236E-23 cgl3999188 chr2 175548310 0.24 1.979E-18 cg02540827 chr2 201221975 0.22 5.035E-21 cgl3651986 chr2 175548447 0.29 8.228E-23 cg04380340 chr2 201450506 0.30 2.419E-24 cg08949655 chr2 176940301 0.25 1.002E-19 cgl3000082 chr2 201450527 0.28 2.19E-18 cg08034440 chr2 176940341 0.23 1.473E-18 cg24569637 chr2 201450560 0.35 1.254E-21 cg07536910 chr2 176948105 0.24 6.833E-18 cg08266417 chr2 201450575 0.38 3.704E-25 cg01749491 chr2 176948693 0.26 5.497E-16 cg09729613 chr2 201450601 0.33 2.489E-20 cgll359133 chr2 176948699 0.22 4.298E-15 cg08952506 chr2 201450610 0.33 1.801E-25 cgl4118515 chr2 176948728 0.26 1.074E-16 cg02657832 chr2 201450633 0.24 5.038E-22 cg07411620 chr2 176948759 0.21 1.578E-15 cg02144933 chr2 201450690 0.28 6.023E-20 cgl7495715 chr2 176950273 0.23 6.974E-22 cgl2627583 chr2 201450731 0.33 6.06E-21 cgll523712 chr2 176957055 0.26 2.287E-22 cgl3875120 chr2 201450743 0.36 9.468E-19 cgl4230696 chr2 176968920 0.28 4.976E-21 cgl4383422 chr2 201450962 0.34 1.373E-18 cg21821214 chr2 176969223 0.21 5.381E-18 cg00857907 chr2 202896898 0.28 7.561E-18 cg26091021 chr2 177021826 0.23 4.532E-19 cg03345454 chr2 202901428 0.22 3.316E-17 cg02773086 chr2 177027440 0.22 1.052E-18 cg00751021 chr2 206474068 0.28 2.309E-20 cg00893471 chr2 177029921 0.22 9.698E-18 cgl7102205 chr2 208091961 0.21 1.248E-16 cg05864326 chr2 177030150 0.27 2.864E-17 cg00458932 chr2 208199465 0.22 4.275E-25 cgl4666564 chr2 177030228 0.22 2.756E-18 cgl5965190 chr2 208370032 0.21 9.076E-21 cgl2602409 chr2 177039568 0.27 1.023E-16 cg20824989 chr2 208491939 0.26 2.747E-18

_

cgl9997502 chr2 208492057 0.30 2.99E-19 cg23807890 chr2 228736357 0.22 1.142E-17 cg27517968 chr2 208546083 0.21 3.635E-16 cg04293526 chr2 231730788 0.27 5.562E-20 cg22346476 chr2 208546089 0.22 5.182E-16 cgl8665334 chr2 231735434 0.20 2.17E-25 cg22399133 chr2 208989248 0.39 1.344E-19 cg07929768 chr2 232055508 0.21 1.645E-15 cg23405212 chr2 208989382 0.27 4.763E-19 cgl2162377 chr2 232261007 0.31 1.4E-21 cgll058366 chr2 213401195 0.22 4.183E-14 cg23052826 chr2 232479675 0.20 4.822E-15 cg00326719 chr2 213401544 0.20 1.262E-14 cg05137450 chr2 233368263 0.21 5.102E-14 cgl7033080 chr2 217508851 0.20 2.549E-22 cgl4192401 chr2 233368543 0.27 1.679E-21 cg09548780 chr2 218770270 0.21 4.725E-23 cg05875017 chr2 233390771 0.21 2.049E-19 cg27369013 chr2 219472724 0.23 4.116E-20 cg23645199 chr2 233498625 0.20 4.738E-19 cg03460682 chr2 219646316 0.22 1.708E-15 cgl0625533 chr2 233498682 0.25 1.525E-19 cgl0147666 chr2 219646481 0.27 7.062E-15 cg02806452 chr2 233499070 0.30 2.742E-20 cgl4553243 chr2 219646657 0.32 3.239E-14 cg05020252 chr2 233499283 0.26 3.966E-18 cg20601919 chr2 219646831 0.46 4.101E-15 cgl8572413 chr2 233741639 0.29 6.427E-22 cg26175971 chr2 219647167 0.20 2.97E-16 cgl4345131 chr2 233741790 0.21 7.528E-23 cg26104932 chr2 219647360 0.26 1.995E-15 cgl3759905 chr2 233741920 0.22 1.121E-24 cg02930667 chr2 219671206 0.25 3.584E-19 cg04621728 chr2 234934131 0.23 8.495E-21 cg05985303 chr2 219723705 0.22 4.146E-21 cg05308656 chr2 235406291 0.22 2.036E-23 cgll511777 chr2 219725959 0.23 7.905 E- 24 cg07014673 chr2 237078733 0.27 8.357E-15 cg05402599 chr2 219846796 0.31 1.687E-17 cg03231647 chr2 237081650 0.21 3.558E-23 cg26830038 chr2 219846925 0.23 3.748E-17 cgl7397592 chr2 237416338 0.20 3.995E-18 cg00260634 chr2 219847233 0.30 5.748E-21 cgl2463851 chr2 237477186 0.20 2.336E-16 cg08396863 chr2 220117599 0.22 1.042E-20 cgl8141622 chr2 238525524 0.20 6.126E-19 cg08378442 chr2 220117704 0.28 1.366E-20 cg26271045 chr2 238535754 0.22 2.68E-17 cgl6725050 chr2 220117771 0.31 9.61E-20 cg01786048 chr2 239035964 0.20 1.023E-18 cgll348442 chr2 220117784 0.27 6.526E-17 cg23497383 chr2 239140182 0.24 1.244E-17 cgl9074496 chr2 220117868 0.27 6.665E-18 cgl3530938 chr2 239140190 0.24 4.654E-19 cg23108728 chr2 220117875 0.24 2.006E-16 cg21272465 chr2 239140296 0.20 1.609E-15 cg08640923 chr2 220117945 0.36 1.985E-16 cg01377268 chr2 239925497 0.20 9.696E-19 cg03970036 chr2 220174232 0.27 8.216E-18 cg26767974 chr2 240143979 0.24 3.093E-20 cg01382864 chr2 220174251 0.22 1.069E-15 cgl5978561 chr2 240196996 0.21 2.671E-17 cg21117965 chr2 220325369 0.27 4.258E-23 cg08276645 chr2 241459502 0.23 4.794E-20 cg07160871 chr2 221969259 0.21 1.542E-15 cg06476685 chr2 241459638 0.23 1.196E-18 cg05736236 chr2 222435214 0.25 1.351E-21 cgl6909733 chr2 241459847 0.23 7.748E-23 cg01446950 chr2 222435351 0.23 3.619E-22 cg25834415 chr2 241758805 0.25 2.429E-17 cg04688351 chr2 223154140 0.24 1.622E-17 cg06546066 chr2 241856000 0.24 3.305E-14 cgl8406033 chr2 223159869 0.23 1.179E-18 cg22367310 chr2 241856114 0.23 1.057E-18 cg08431536 chr2 223161894 0.23 2.799E-17 cgl4396008 chr2 241856143 0.22 4.895E-14 cg25596297 chr2 223162875 0.22 6.635E-16 cg04874782 chr2 241900108 0.27 8.991E-21 cg06916239 chr2 223162881 0.24 6.527E-16 cg26707709 chr2 241975756 0.20 3.078E-20 cg23546474 chr2 223163033 0.21 1.081E-15 cg22635676 chr2 241975971 0.26 3.937E-18 cg09424526 chr2 223163809 0.20 1.104E-17 cg02639108 chr2 242711009 0.21 6.971E-17 cgl6529477 chr2 223164854 0.23 1.947E-17 cg20805133 chr2 242802192 0.21 1.937E-18 cgl8077971 chr2 223164867 0.28 1.043E-17 cgll229343 chr2 242808427 0.22 7.896E-16 cg01841641 chr2 223169965 0.20 4.654E-17 cg05507490 chr2 242808479 0.27 4.023E-16 cg02099878 chr2 223176167 0.24 1.266E-16 cgl0277651 chr20 623361 0.23 8.747E-18 cg00514407 chr2 224904626 0.21 2.282E-16 cgl8803306 chr20 623421 0.21 2.284E-19 cg01833675 chr2 225266876 0.21 6.695E-16 cg02751731 chr20 642436 0.22 1.057E-22 cg05209518 chr2 227288518 0.22 1.687E-20 cg20543681 chr20 642673 0.27 8.264E-24 cg25713185 chr2 228582486 0.24 9.294E-19 cg01235820 chr20 642782 0.33 9.392E-23 cg07417745 chr2 228582488 0.27 1.948E-20 cg26282655 chr20 2505978 0.20 8.934E-17 cg23122109 chr2 228582688 0.22 1.463E-16 cg07341624 chr20 2539167 0.21 7.879E-19 cg00063174 chr2 228736253 0.29 1.122E-17 cg09774842 chr20 3052483 0.21 6.921E-16 cg20647610 chr2 228736258 0.30 6.726E-18 cg06404175 chr20 3052692 0.26 4.517E-15 cg08034379 chr2 228736324 0.23 8.98E-17 cgl2099952 chr20 3053037 0.26 6.358E-21

cg21304453 chr20 3218794 0.27 2.507E-21 cg03356734 chr20 37230413 0.24 3.664E-23 cgl0748765 chr20 3218905 0.26 1.048E-17 cg06301550 chr20 37230484 0.28 3.62E-19 cg01996714 chr20 3220839 0.26 4.444E-23 cgl3802013 chr20 37303351 0.22 1.023E-21 cg00858599 chr20 3220929 0.24 2.892E-24 cg04961101 chr20 37303484 0.21 1.506E-16 cg27647152 chr20 3220985 0.22 2.874E-23 cg07906520 chr20 37435716 0.32 1.973E-23 cgl0322504 chr20 3229239 0.20 4.159E-15 cgl6529599 chr20 42137055 0.25 6.895E-20 cgl6818740 chr20 4803300 0.29 3.657E-17 cg00393825 chr20 42137061 0.22 2.586E-18 cgll988831 chr20 4803490 0.25 4.938E-19 cg06962944 chr20 42544728 0.21 1.178E-14 cgl6831623 chr20 6750617 0.22 1.998E-18 cg26040816 chr20 42816135 0.24 3.957E-18 cgl8039133 chr20 6750956 0.22 2.724E-17 cgl2689285 chr20 42875765 0.24 8.027E-22 cg09143713 chr20 9141615 0.23 2.523E-21 cg04448487 chr20 42875777 0.27 3.692E-20 cgl7227967 chr20 9496556 0.30 3.3E-19 cg09994356 chr20 42875779 0.35 2.313E-20 cgl7368808 chr20 9496892 0.22 8.634E-17 cg07160746 chr20 43726765 0.24 3.274E-15 cgl7466795 chr20 9497330 0.24 5.804E-23 cgll626007 chr20 43743835 0.22 5.553E-24 cgll525020 chr20 17674233 0.21 8.52E-19 cg03172947 chr20 44035850 0.28 9.965E-23 cg25959149 chr20 17674250 0.21 2.189E-20 cg00929635 chr20 44035918 0.27 4.851E-21 cgl4646111 chr20 18489660 -0.21 1.015E-20 cg00700485 chr20 44098223 0.30 8.831E-26 cg08755224 chr20 21001116 0.21 4.556E-19 cg25799986 chr20 44098281 0.27 8.122E-24 cg04792330 chr20 21001266 0.28 1.486E-19 cg21963535 chr20 44098285 0.32 4.394E-26 cg25881804 chr20 21081901 0.26 3.997E-16 cg06385187 chr20 44098287 0.36 2.569E-24 cgl9709468 chr20 21082942 0.21 2.058E-17 cg26348514 chr20 44098358 0.27 3.387E-24 cgl4262681 chr20 21084420 0.41 5.671E-17 cg23740882 chr20 44098387 0.37 1.432E-26 cg01513392 chr20 21488198 0.21 3.639E-22 cgl4151783 chr20 44098409 0.42 7.891E-24 cg08183724 chr20 21497429 0.24 2.517E-16 cg00980978 chr20 44098724 0.38 6.805E-27 cgl7651959 chr20 21498100 0.27 1.38E-18 cg27150417 chr20 44462035 0.25 2.018E-21 cg22749589 chr20 21501710 0.21 8.214E-16 cg08260891 chr20 44518802 0.22 2.165E-15 cg07676859 chr20 23015932 0.25 9.131E-17 cg24182521 chr20 44541013 0.22 1.336E-20 cg22534145 chr20 23015936 0.22 2.044 E- 16 cg06132069 chr20 44686038 0.23 1.584E-15 cg04299389 chr20 25129296 0.32 2.678E-18 cg01460436 chr20 44687454 0.22 9.4E-19 cgl8009321 chr20 25129457 0.26 8.79E-19 cgll841529 chr20 44746751 0.21 6.788E-15 cgll724135 chr20 25129507 0.28 1.104E-16 cg06571407 chr20 44746823 0.21 1.506E-17 cg22645427 chr20 25129520 0.28 3.61E-17 cg22232207 chr20 44746825 0.21 6.738E-17 cg05908371 chr20 25129529 0.21 3.252E-16 cgl6686951 chr20 44747351 0.20 1.451E-17 cgl6265348 chr20 25129542 0.21 2.709E-17 cg06263461 chr20 45280237 0.32 7.449E-21 cg08941457 chr20 25129562 0.26 2.621E-20 cgl3551814 chr20 45280276 0.22 1.817E-20 cg03522245 chr20 25566470 0.24 3.42E-15 cgl9421368 chr20 45280288 0.22 1.585E-18 cgl6686733 chr20 25566563 0.23 2.239E-17 cg01906944 chr20 45439769 0.21 6.259E-21 cg01408508 chr20 26188639 0.26 8.51E-16 cgl8069125 chr20 45439836 0.29 3.503E-23 cg04150495 chr20 26190328 0.24 1.74E-16 cg07400877 chr20 45440085 0.27 2.414E-21 cg20395967 chr20 26190347 0.22 3.692E-16 cg07724670 chr20 45440228 0.29 2.808E-22 cgl0715092 chr20 26190354 0.26 1.972E-15 cg24874350 chr20 45440346 0.27 1.004E-21 cg01338255 chr20 30176054 0.23 1.368E-17 cg06260709 chr20 48626621 0.24 1.399E-20 cg08340755 chr20 30176106 0.20 6.015E-17 cgl5409939 chr20 48789081 0.21 1.307E-17 cg09044785 chr20 30458634 0.23 4.475E-19 cg04109822 chr20 50158057 0.28 3.092E-22 cg06102403 chr20 30458708 0.28 1.369E-20 cg02991469 chr20 50720731 0.26 8.411E-18 cg03513363 chr20 30458745 0.28 3.464E-21 cg25480336 chr20 50720908 0.33 1.032E-17 cg09775533 chr20 32857151 0.26 8.415E-15 cgl4032025 chr20 50721129 0.32 1.591E-19 cg03547924 chr20 34025927 0.21 6.824E-17 cg00727630 chr20 50721366 0.27 7.005E-22 cg22289434 chr20 34188940 0.26 3.895E-20 cg01529637 chr20 50721911 0.23 9.294E-17 cgl8660345 chr20 35169539 0.22 9.034E-18 cgll903133 chr20 50722613 0.29 5.39E-16 cg03191045 chr20 36040903 0.31 8.576E-24 cgl9035232 chr20 51589985 0.31 5.084E-15 cg20859731 chr20 36226820 0.21 3.715E-18 cgl8881873 chr20 52276947 0.28 4.422E-20 cg01025836 chr20 37230326 0.28 8.515E-19 cg21251385 chr20 52277050 0.25 3.805E-17 cg00557360 chr20 37230386 0.25 2.747E-19 cg20779964 chr20 54580070 0.26 2.245E-17 cg04608177 chr20 37230389 0.22 3.71E-19 cg27563985 chr20 54580677 0.26 6.657E-17

_

cgl8759209 chr20 55842071 0.27 1.62E-21 cg04285033 chr21 46143498 0.35 4.597E-18 cg25249539 chr20 56803358 0.22 4.166E-18 cg25020459 chr21 47402144 0.29 9.895E-18 cg09676129 chr20 60540388 0.23 4.041E-18 cg02776659 chr21 47717406 0.26 1.051E-20 cg00152041 chr20 61274867 0.24 2.614E-18 cg20399509 chr21 47717575 0.29 1.323E-17 cg00199007 chr20 61583910 0.24 3.686E-14 cg00612595 chr21 47717864 0.24 5.944E-17 cgl6552454 chr20 61583924 0.22 1.304E-14 cg00815214 chr21 47717953 0.21 3.175E-20 cg04478428 chr20 61584072 0.23 3.743E-16 cgl2516959 chr21 47718080 0.23 3.442E-19 cg01817521 chr20 61584108 0.27 6.386E-16 cgl2441967 chr22 17602561 0.26 2.239E-22 cg26733301 chr20 61585924 0.25 6.253E-22 cg22059073 chr22 17602570 0.24 9.543E-25 cg26186239 chr20 62119492 0.22 3.259E-18 cg06561329 chr22 17602610 0.29 2.156E-23 cg01176363 chr20 62369445 0.25 1.876E-14 cg21872764 chr22 19510977 0.22 4.528E-14 cg21849932 chr20 62369462 0.22 5.417E-15 cg09092054 chr22 19511987 0.20 1.271E-14 cg01582438 chr20 62461159 0.26 5.183E-23 cg20486569 chr22 19512228 0.35 4.564E-22 cg05269938 chr20 62461294 0.38 6.156E-22 cg09938462 chr22 19706365 0.25 3.125E-14 cgl2002882 chr20 62461365 0.24 3.515E-22 cg08886651 chr22 19743029 0.25 1.525E-15 cg26788916 chr20 62461539 0.23 9.056E-21 cg00204782 chr22 19753364 0.20 1.816E-19 cgl5580304 chr20 62550734 -0.25 2.539E-16 cgl9601636 chr22 20001066 0.20 4.807E-22 cg24348495 chr20 62693971 0.21 5.301E-16 cg27657537 chr22 20863762 0.21 1.399E-20 cg03946671 chr20 62693973 0.24 2.123E-16 cg07153010 chr22 21312388 0.38 3.693E-25 cgl2176783 chr20 62694000 0.32 2.76E-20 cg01763749 chr22 21368291 0.26 2.224E-20 cgl9266578 chr20 62711729 0.22 3.095E-17 cg27645955 chr22 21386885 0.22 2.951E-14 cgl8128969 chr21 22369908 0.26 5.402E-20 cg23644624 chr22 21386989 0.22 6.233E-15 cgl9556343 chr21 22370046 0.22 3.837E-18 cgl3879495 chr22 22005669 0.24 1.089E-16 cgl3297960 chr21 22370237 0.26 1.28E-18 cgll673244 chr22 22007100 0.23 3.311E-20 cg23720384 chr21 23747055 0.25 1.158E-20 cgl6835233 chr22 22862479 0.23 3.877E-18 cg09704750 chr21 27011139 0.23 8.194E-17 cgl9764436 chr22 23413260 0.23 7.101E-22 cgl5853125 chr21 32932267 0.23 8.891E-18 cg25349820 chr22 25346354 0.21 5.018E-19 cg06212263 chr21 34392851 0.22 1.034E-14 cg21347353 chr22 25678439 0.21 9.564E-16 cg09793121 chr21 34398263 0.21 7.221E-15 cg27045447 chr22 28198218 0.26 8.454E-17 cg22869726 chr21 34398265 0.25 1.165E-15 cgl7326090 chr22 28198472 0.25 3.093E-20 cg06106763 chr21 34444104 0.24 4.066E-14 cg21687563 chr22 28838019 0.25 4.726E-19 cg22212414 chr21 34775032 0.27 1.253E-14 cg06969287 chr22 28838631 0.29 6.168E-25 cg24865779 chr21 34775042 0.30 4.517E-15 cg27422872 chr22 28839137 0.36 1.847E-20 cgl0572943 chr21 34775045 0.25 3.411E-14 cg04294888 chr22 28839249 0.40 2.27E-25 cgl7935217 chr21 36042170 0.35 1.351E-15 cg26480862 chr22 28839667 0.30 1.281E-23 cgll498607 chr21 36399226 0.20 4.578E-18 cgl2552771 chr22 29709320 0.25 9.195E-20 cg04228935 chr21 36399258 0.23 9.138E-17 cg25937577 chr22 31536476 0.24 2.256E-19 cg02413040 chr21 36419648 0.20 1.966E-18 cg05815196 chr22 31536540 0.26 5.638E-20 cgl2426652 chr21 37915056 0.24 9.319E-20 cg00727590 chr22 31536549 0.20 7.599E-21 cg04965987 chr21 38378539 0.24 3.766E-19 cgl4586373 chr22 37447398 0.23 4.657E-18 cgl6886987 chr21 38378634 0.24 2.134E-17 cgl5909981 chr22 37465178 0.22 5.57E-16 cgl8566883 chr21 38919676 0.22 2.892E-16 cg05226932 chr22 37720696 0.22 1.956E-17 cgl9788186 chr21 39669558 0.20 1.993E-22 cg20351171 chr22 37720723 0.24 1.031E-20 cg00397324 chr21 42798594 0.29 2.526E-15 cg22564583 chr22 37720976 0.26 3.21E-17 cg08924203 chr21 42798747 0.29 2.474E-16 cgl9406182 chr22 37721149 0.29 3.766E-16 cg24128931 chr21 44013597 0.20 6.528E-16 cgll586832 chr22 37721305 0.25 5.491E-18 cg04090347 chr21 44061597 0.21 5.322E-20 cg21737444 chr22 38071591 0.23 3.359E-20 cg25191041 chr21 44782470 0.25 2.239E-19 cg25247183 chr22 38073049 0.31 1.115E-17 cgl4081667 chr21 44782497 0.22 2.023E-17 cg02527527 chr22 38303310 0.23 3.595E-19 cgl5777964 chr21 44847606 0.24 4.079E-18 cgl9414598 chr22 38965745 0.27 1.41E-17 cg07494518 chr21 44847608 0.22 4.724E-19 cgl0316474 chr22 39410068 0.22 2.548E-26 cg08692423 chr21 45148864 0.22 9.373E-16 cgl9713460 chr22 39745530 0.27 5.682E-20 cg01907098 chr21 45149141 0.21 1.073E-17 cg22471255 chr22 42315642 0.24 4.353E-16 cg02074274 chr21 45178331 0.22 2.802E-20 cg00305281 chr22 42316176 0.21 4.621E-19 cg22991148 chr21 46131099 0.27 1.57E-19 cg25219329 chr22 42679444 0.21 1.85E-21

_

cgl7568996 chr22 42828125 0.28 9.157E-25 cg02499249 chr3 25469720 0.27 7.322E-24 cg08690876 chr22 43040721 0.23 9.721E-24 cg24396624 chr3 25469860 0.41 5.425E-24 cg25044876 chr22 43041146 0.24 1.226E-20 cg26786980 chr3 25469872 0.36 2.137E-24 cg26453588 chr22 43506021 0.21 1.606E-23 cgl9003815 chr3 25469914 0.29 2.282E-21 cg04042468 chr22 43506033 0.29 1.754E-20 cg27486427 chr3 25469919 0.27 4.276E-23 cgl0820551 chr22 45608345 0.20 8.455E-21 cg03428864 chr3 25469925 0.25 6.124E-21 cg04223044 chr22 45608428 0.22 1.204E-21 cgl6927871 chr3 25469991 0.27 3.598E-22 cgl2251779 chr22 45608440 0.22 3.388E-21 cg26263234 chr3 26666060 0.22 1.216E-15 cg22488367 chr22 45608448 0.24 1.698E-21 cg21473142 chr3 27762095 0.21 4.164E-15 cg21935981 chr22 45608465 0.24 3.134E-22 cgl5540820 chr3 27765283 0.22 3.906E-19 cg07795766 chr22 45608516 0.24 2.106E-21 cgll642106 chr3 27772805 0.22 3.268E-19 cg02099543 chr22 45899186 0.23 3.416E-16 cg06568535 chr3 29323042 0.21 3.452E-18 cg08149253 chr22 45899292 0.21 7.417E-16 cgl9142043 chr3 29724842 0.21 5.304E-20 cg02287693 chr22 46276479 0.20 2.112E-16 cg00744866 chr3 33701209 0.25 1.823E-18 cg23858410 chr22 46276678 0.21 3.325E-15 cg09866743 chr3 35706038 0.24 2.857E-18 cgl5879316 chr22 46934089 0.20 4.617E-18 cgl5571561 chr3 35706161 0.27 2.79E-19 cg06866938 chr22 46934811 0.24 3.342E-24 cg24144083 chr3 36805814 0.26 9.862E-20 cg25423416 chr22 46934860 0.22 5.074E-26 cgl5934958 chr3 37212084 0.26 1.409E-18 cgll533712 chr22 46934981 0.21 8.176E-21 cgl3071386 chr3 37494403 0.20 5.379E-18 cgl9796981 chr22 50438501 0.29 2.373E-19 cgl2902896 chr3 37987838 0.22 6.21E-23 cgl4913695 chr22 50449520 0.26 6.682E-19 cg02254461 chr3 39195904 0.22 3.445E-22 cg05297854 chr22 50623687 0.25 2.354E-17 cgl7264618 chr3 40429014 0.22 5.777E-15 cgll213574 chr22 50623692 0.24 2.013E-16 cgl2084388 chr3 42056663 0.22 1.88E-18 cg08260245 chr22 51016501 0.21 5.435E-17 cg22222413 chr3 42066796 0.21 8.034E-19 cg06530441 chr22 51016950 0.21 8.604E-17 cgl9230867 chr3 42103367 0.22 1.244E-19 cg26201811 chr22 51111714 0.23 1.756E-21 cg21821833 chr3 42306493 0.22 1.164E-14 cgl7567700 chr22 51112218 0.22 1.765E-17 cglll42705 chr3 42306974 0.33 1.808E-17 cgl0208485 chr3 350602 0.23 1.578E-14 cgl4858267 chr3 44037760 0.27 9.318E-19 cgl0901633 chr3 4814459 0.21 2.186E-21 cg26365925 chr3 44063315 0.21 3.562E-19 cgl6582517 chr3 5025885 0.22 1.167E-21 cg03795847 chr3 44596512 0.23 6.473E-20 cg09881545 chr3 5137630 0.28 6.077E-24 cg22598028 chr3 44626492 0.28 7.908E-15 cg07351192 chr3 5137773 0.27 3.455E-22 cgl7536166 chr3 44626697 0.22 4.476E-16 cgl9385628 chr3 6904640 0.23 1.626E-14 cgl5688619 chr3 44626860 0.21 2.114E-18 cg00907288 chr3 9178249 0.21 7.454E-15 cgl6975587 chr3 46506206 0.20 2.279E-19 cg21386647 chr3 9289893 0.22 4.834E-20 cgl5261665 chr3 46506374 0.21 1.174E-21 cg04377609 chr3 9358914 0.20 6.762E-22 cg26307117 chr3 46506552 0.21 8.038E-23 cg07220922 chr3 10806022 0.26 1.615E-20 cg02534363 chr3 47050950 0.28 3.263E-16 cgl8096987 chr3 11623873 0.20 3.622E-16 cg09354556 chr3 47051341 0.27 1.501E-22 cg07330114 chr3 11624023 0.29 2.134E-20 cg22292345 chr3 47051533 0.21 1.454E-18 cgl3878677 chr3 13060915 0.23 6.876E-20 cg24257776 chr3 47051546 0.22 1.974E-18 cgl3526469 chr3 13245693 0.24 3.665E-17 cgll846236 chr3 48632568 0.25 3.831E-20 cgl5275625 chr3 13343118 0.23 3.62E-24 cgl7913386 chr3 48632582 0.26 1.533E-18 cgl0633526 chr3 13560246 0.20 4.669E-20 cg00158683 chr3 48632625 0.25 5.797E-17 cg25457886 chr3 14339565 0.25 6.671E-16 cg08772752 chr3 48632672 0.21 1.776E-15 cgl8038544 chr3 14576099 0.25 2.516E-23 cgl4957943 chr3 48632783 0.21 5.202E-16 cg25223095 chr3 16927003 0.25 3.02E-21 cg05924489 chr3 49459937 0.21 6.774E-19 cg02923856 chr3 23989124 0.20 5.812E-20 cgl4957718 chr3 50243260 0.26 3.529E-15 cg00371702 chr3 25469125 0.23 6.236E-21 cgl9755318 chr3 50243323 0.22 4.092E-17 cg00758229 chr3 25469148 0.24 3.545E-19 cg04743654 chr3 50378292 0.26 8.407E-17 cg20899354 chr3 25469392 0.30 1.399E-16 cgl2966367 chr3 50378407 0.23 3.648E-19 cg26124016 chr3 25469402 0.31 1.04E-15 cg21554552 chr3 50378425 0.21 2.175E-18 cgl8094781 chr3 25469430 0.29 2.647E-17 cg27569446 chr3 50378431 0.22 2.857E-14 cgl2479047 chr3 25469573 0.27 4.44E-18 cg25486143 chr3 50378527 0.22 2.779E-16 cg06720425 chr3 25469694 0.23 1.429E-22 cg09451427 chr3 50488230 0.24 2.107E-14 cg03481274 chr3 25469708 0.38 3.185E-25 cg06637517 chr3 52407344 0.28 3.31E-17

cgl6438525 chr3 52517742 0.20 4.978E-20 cgll980129 chr3 79815639 0.21 1.553E-19 cg00345443 chr3 54121778 0.21 5.13E-17 cg04562217 chr3 79815718 0.23 1.706E-17 cgl2173409 chr3 54154746 0.21 5.644E-18 cgl4611399 chr3 87138203 0.22 2.072E-17 cg23537887 chr3 54157647 0.23 1.376E-18 cg21741562 chr3 87138387 0.31 9.225E-17 cg06678678 chr3 55523099 0.24 2.496E-18 cg03660115 chr3 87138400 0.29 2E-17 cg04394267 chr3 55523950 0.23 3.58E-14 cgl6856833 chr3 87138640 0.27 2.162E-21 cg25119690 chr3 55524048 0.21 9.123E-15 cg00169617 chr3 87138700 0.29 5.291E-20 cgl4936968 chr3 57198533 0.39 1.273E-20 cg00210994 chr3 99594893 0.23 4.323E-16 cgl9764345 chr3 57198797 0.34 8.047E-18 cgl5963552 chr3 99594931 0.32 2.832E-16 cg24033633 chr3 57945695 0.22 3.442E-17 cg20276377 chr3 99595026 0.31 8.275E-16 cg22012981 chr3 58522689 0.21 3.029E-22 cg22092811 chr3 99595145 0.26 6.399E-16 cgl6587010 chr3 58523130 0.25 2.759E-21 cgl8337222 chr3 99595254 0.21 1.151E-19 cgl3705284 chr3 58523313 0.22 5.427E-22 cg00991994 chr3 99639553 0.21 2.712E-22 cg23069167 chr3 61550379 0.29 6.6E-18 cgl9401033 chr3 107148372 0.21 2.971E-18 cg01861913 chr3 61550569 0.25 8.374E-22 cgl0777851 chr3 112051808 0.25 1.112E-18 cg24008577 chr3 62353504 0.21 3.404 E- 18 cg01031032 chr3 112051894 0.21 6.646E-16 cg21148362 chr3 62353708 0.27 1.372E-14 cg03329165 chr3 112052218 0.24 5.772E-19 cg27088150 chr3 62353894 0.24 3.256E-19 cg07251099 chr3 112052405 0.26 3.567E-18 cg03308652 chr3 62354991 0.20 1.625E-17 cgll205552 chr3 112995690 0.23 4.591E-18 cg00503302 chr3 62355319 0.26 2.425E-17 cg00491927 chr3 120003642 0.21 4.551E-17 cgl2378187 chr3 62355443 0.24 2.886E-16 cg04135498 chr3 120628544 0.21 3.809E-18 cgl2988424 chr3 62355884 0.21 6.035E-19 cg07629454 chr3 121903520 0.23 3.995E-15 cg20072171 chr3 62356962 0.37 6.496E-17 cgl8016254 chr3 122296505 0.22 4.974E-22 cgl8525486 chr3 62357176 0.22 4.357E-18 cgl9166302 chr3 122296613 0.31 4.213E-22 cg08252579 chr3 62359773 0.21 6.384E-18 cg04564920 chr3 122296778 0.25 4.634E-20 cg08681924 chr3 62359924 0.28 3.425E-17 cg02586610 chr3 122745092 0.27 1.917E-19 cg24945701 chr3 62362783 0.26 7.848E-19 cg26105015 chr3 122745099 0.26 5.976E-20 cg08994384 chr3 62363642 0.22 5.666E-16 cgll483789 chr3 122745560 0.23 2.116E-16 cgl3720108 chr3 62364032 0.27 3.566E-19 cg20669834 chr3 123339417 0.22 1.162E-23 cgl8450254 chr3 64200005 0.26 5.267E-20 cg00465319 chr3 123339568 0.22 5.928E-21 cgl5310857 chr3 64253534 0.27 1.277E-22 cg07621385 chr3 123535716 0.23 4.718E-22 cg05063999 chr3 64253605 0.31 2.917E-22 cg00268185 chr3 123602768 0.27 1.363E-19 cgll610350 chr3 64253705 0.27 1.357E-21 cg27345757 chr3 123602795 0.22 1.159E-18 cg23170347 chr3 64253795 0.24 2.327E-23 cgl2788878 chr3 124860616 0.26 1.498E-19 cg21456897 chr3 64253803 0.25 1.262E-22 cg26107890 chr3 124860686 0.29 1.973E-18 cg08275638 chr3 64253818 0.24 1.359E-20 cg04844977 chr3 125691054 0.23 7.829E-17 cg22081832 chr3 64670459 0.23 1.638E-17 cg07034362 chr3 125899552 0.23 4.311E-16 cg25859972 chr3 64670515 0.26 3.612E-19 cgll022432 chr3 125899878 0.38 2.432E-22 cg26061177 chr3 64670562 0.23 2.779E-19 cgl6771578 chr3 125899895 0.36 2.158E-22 cg07891473 chr3 64670640 0.23 7.957E-21 cg02569236 chr3 125899915 0.22 7.759E-23 cg04421973 chr3 64670907 0.24 6.135E-19 cg07330230 chr3 125899925 0.38 1.009E-25 cgl8697991 chr3 64823081 0.21 5.104E-20 cg21601837 chr3 125900065 0.30 1.294E-24 cgl3475665 chr3 65582925 0.25 1.309E-16 cg20988073 chr3 125900093 0.24 7.871E-23 cg02090033 chr3 65583617 0.21 1.101E-14 cg08481491 chr3 125900108 0.24 3.603E-22 cg01405004 chr3 68980539 0.26 3.626E-23 cg07118796 chr3 126892022 0.24 7.043E-20 cg03186486 chr3 68980947 0.30 1.416E-21 cgl4212504 chr3 128564815 0.20 1.39E-15 cgl5356923 chr3 68981011 0.33 1.727E-23 cg07398614 chr3 128564918 0.30 3.438E-18 cg20743134 chr3 69061356 0.24 2.145E-21 cgl5676455 chr3 128564943 0.26 4.695E-20 cg08555612 chr3 71834640 0.22 1.747E-16 cgl8531004 chr3 128564980 0.31 4.956E-23 cgl0935662 chr3 72307754 0.23 1.195E-22 cgl9129842 chr3 128565090 0.26 7.056E-23 cgll278506 chr3 72787955 0.25 2.449E-19 cg00112465 chr3 128719999 0.23 5.004E-15 cg04365224 chr3 72788183 0.33 4.748E-17 cg04467162 chr3 128764824 0.20 1.317E-17 cg27402429 chr3 72788294 0.27 2.401E-19 cg08425203 chr3 128764940 0.22 1.886E-18 cgl0804678 chr3 72788309 0.23 1.215E-19 cg20264543 chr3 128787213 0.20 9.53E-20 cg00842687 chr3 73816009 0.21 1.05E-20 cg00465970 chr3 129024601 0.25 2.497E-20

cg23245007 chr3 195682326 0.25 7.341E-19 cg07333191 chr4 13526769 0.23 4.838E-18 cgl7172980 chr3 196755973 0.31 3.983E-23 cgl7922359 chr4 13530923 0.22 1.772E-19 cg05143530 chr3 197439242 0.26 2.798E-18 cgl9019849 chr4 13533145 0.22 3.942E-19 cg03367387 chr3 197439334 0.28 1.809E-20 cgl6297011 chr4 13539023 0.26 2.654E-19 cgl7121747 chr4 683060 0.27 6.333E-17 cgl2973941 chr4 13545639 0.27 2.56E-16 cg07434284 chr4 779691 0.27 1.584E-21 cgl9852958 chr4 13545760 0.23 4.16E-16 cgl7397631 chr4 779880 0.31 5.404E-22 cgl5175162 chr4 15657657 0.20 1.122E-18 cg27651229 chr4 780336 0.26 1.948E-21 cg00731785 chr4 15704680 0.28 1.65E-15 cg22718636 chr4 961658 0.24 1.551E-19 cgl2839172 chr4 16085077 0.24 4.185E-17 cg09223687 chr4 1027885 0.20 3.872E-18 cgl3164157 chr4 16085180 0.30 5.522E-20 cg08954277 chr4 1535673 0.21 8.334E-16 cg07817686 chr4 16085401 0.23 1.301E-18 cg00626702 chr4 1647016 0.25 2.665E-20 cg09024126 chr4 16085603 0.36 1.473E-20 cgl9300568 chr4 2060112 0.30 1.227E-20 cgl4736058 chr4 16085606 0.35 1.459E-19 cgl0219157 chr4 2395549 0.23 2.624E-17 cgl0630155 chr4 16085666 0.25 1.295E-21 cg24492202 chr4 2802612 0.23 6.861E-19 cg04203238 chr4 16085702 0.32 5.469E-24 cgl6786640 chr4 3485263 0.30 1.696E-20 cg26260038 chr4 16085716 0.28 4.561E-24 cg25216704 chr4 3485393 0.21 3.676E-18 cg07696699 chr4 17783502 0.32 6.596E-18 cgll852579 chr4 3657880 0.20 3.212E-20 cg03260566 chr4 20256841 0.28 2.87E-16 cgl4039306 chr4 4862240 0.25 1.03E-18 cg02896941 chr4 23890659 0.31 5.036E-18 cg03199651 chr4 4862770 0.24 1.623E-22 cg27182172 chr4 23890890 0.21 3.069E-17 cgl4167596 chr4 4862910 0.23 8.356E-18 cg05158538 chr4 23891486 0.22 5.003E-16 cg22256027 chr4 4863016 0.24 5.801E-20 cgl9766441 chr4 25657365 0.30 4.267E-14 cgl8827954 chr4 5053585 0.25 3.373E-16 cg07578695 chr4 25657414 0.25 2.36E-14 cg05571820 chr4 5709858 0.24 7.148E-16 cgl5657686 chr4 37978666 0.31 5.93E-22 cgl4654886 chr4 5710319 0.30 4.65E-16 cg24651977 chr4 37978758 0.30 4.063E-21 cg27434509 chr4 5710337 0.31 2.338E-16 cgl5032098 chr4 41258560 0.21 9.174E-17 cgl7255450 chr4 5710372 0.31 2.237E-18 cg07068756 chr4 41258910 0.30 1.307E-15 cg06426416 chr4 5710403 0.34 5.701E-19 cgl6142306 chr4 41258935 0.22 4.953E-17 cg05542338 chr4 5710407 0.29 5.155E-18 cgl6026922 chr4 41259044 0.22 9.407E-15 cg01834022 chr4 5710411 0.34 1.055E-17 cg25349276 chr4 41614591 0.22 5.465E-22 cg23893898 chr4 6247571 0.24 7.094E-19 cg00957901 chr4 41614842 0.22 7.579E-24 cg06424065 chr4 6247640 0.23 1.931E-19 cg20438306 chr4 41747092 0.27 2.257E-21 cg02556634 chr4 6449000 0.21 3.994E-21 cg07907386 chr4 41749443 0.23 5.697E-17 cg00497232 chr4 6665905 0.22 4.627E-20 cgl4227486 chr4 41867415 0.26 6.228E-23 cg20834178 chr4 6944071 0.21 2.269E-24 cg26871372 chr4 41867517 0.29 2.181E-18 cgl8011273 chr4 7203326 0.21 3.898E-14 cgl6647921 chr4 41867533 0.39 7.382E-22 cgl7949969 chr4 8073790 0.26 1.738E-16 cgll028201 chr4 41867562 0.28 1.345E-20 cg21737039 chr4 8271391 0.24 9.914E-15 cg20963227 chr4 41868203 0.22 2.082E-18 cg09495977 chr4 8271507 0.25 1.765E-14 cgl2929487 chr4 41869175 0.30 7.199E-20 cgl9317600 chr4 8395941 0.21 5.213E-21 cg25585712 chr4 41869213 0.26 1.903E-21 cgl3073564 chr4 8508604 0.22 2.789E-21 cg26195583 chr4 41869348 0.24 7.324E-22 cg26296488 chr4 9783192 0.28 3.222E-17 cg09784335 chr4 41875193 0.25 1.199E-24 cg23847712 chr4 9783196 0.26 3.258E-17 cg05036656 chr4 41875470 0.29 8.866E-20 cg03045635 chr4 9783198 0.26 1.799E-18 cg20885782 chr4 41875606 0.23 4.792E-20 cg25117600 chr4 10023201 0.21 3.804E-19 cg08049853 chr4 41875784 0.24 1.262E-18 cgl5333426 chr4 10463620 0.21 6.804E-18 cg09349604 chr4 41880747 0.20 1.8E-20 cg06745511 chr4 10585774 0.21 1.046E-18 cg24947764 chr4 41881359 0.26 1.93E-20 cg07260927 chr4 11428822 0.23 1.046E-16 cg01871214 chr4 41881417 0.28 7.75E-20 cg01089498 chr4 11428985 0.32 1.835E-18 cg24722073 chr4 41882163 0.24 3.29E-19 cg24431872 chr4 11429036 0.20 2.668E-17 cgl7231999 chr4 41882564 0.35 2.06E-17 cgl4820199 chr4 11429415 0.32 5.985E-24 cg04384626 chr4 41882580 0.25 3.741E-19 cg24029517 chr4 11429531 0.32 2.593E-22 cg01370541 chr4 41882812 0.26 6.36E-20 cg00368055 chr4 11429689 0.28 6.956E-19 cg02881929 chr4 41882868 0.22 1.243E-20 cg25913520 chr4 13524041 0.21 3.739E-15 cg27405791 chr4 41882953 0.21 5.066E-19 cg20291855 chr4 13524143 0.27 1.312E-16 cg24394172 chr4 46995203 0.21 3.724E-17

cg24154839 chr4 46995741 0.27 1.697E-20 cg05121006 chr4 85402397 0.23 7.65E-18 cg25951981 chr4 46995743 0.22 8.378E-21 cgl7071446 chr4 85402497 0.22 2.748E-19 cgl0062193 chr4 47533905 0.23 1.564E-21 cg06065125 chr4 85402870 0.24 1.936E-18 cgl3625875 chr4 54959419 0.29 4.037E-20 cg24882551 chr4 85403032 0.22 1.187E-15 cg26926138 chr4 54960034 0.22 1.074E-18 cg22857085 chr4 85403223 0.22 7.854E-18 cg20233073 chr4 54960226 0.22 3.477E-20 cg25174438 chr4 85403915 0.25 9.624E-19 cgl3117164 chr4 54960232 0.21 3.431E-20 cg03554749 chr4 85405132 0.28 1.47E-16 cg25019989 chr4 54961835 0.22 8.048E-22 cg08474859 chr4 85414016 0.21 2.225E-18 cgl4686113 chr4 54965829 0.29 8.148E-20 cg00316839 chr4 85414135 0.20 2.259E-18 cgl3506653 chr4 54965863 0.42 1.735E-19 cg24845848 chr4 85414873 0.23 1.429E-16 cg21905630 chr4 54965904 0.27 6.095E-18 cg25830182 chr4 85417077 0.26 1.435E-16 cg09632907 chr4 54969963 0.25 5.602E-24 cg02489958 chr4 85417416 0.23 1.091E-18 cg02381898 chr4 54970175 0.26 5.314E-20 cgl2076463 chr4 85418265 0.20 2.623E-18 cg03669782 chr4 54970254 0.24 2.936E-21 cg23254393 chr4 85423132 0.23 2.671E-20 cg02124022 chr4 54974886 0.20 4.962E-21 cg04184019 chr4 85424288 0.24 7.957E-19 cg27543103 chr4 54975677 0.26 1.377E-20 cg21843616 chr4 85424469 0.24 2.167E-20 cgl2630714 chr4 54975894 0.31 2.448E-24 cgl4376467 chr4 86851411 0.24 6.635E-16 cg25054580 chr4 54976019 0.24 3.463E-22 cgl7485454 chr4 87281281 0.21 8.925E-20 cg23999932 chr4 54976184 0.24 1.712E-22 cgl9124509 chr4 87281412 0.29 6.79E-18 cg01166145 chr4 55093692 0.22 1.088E-17 cgl2225220 chr4 87281434 0.28 4.166E-18 cg00691999 chr4 55094011 0.24 1.471E-17 cgl4578894 chr4 87281511 0.27 1.826E-19 cg06483432 chr4 55523233 0.22 2.372E-21 cg08197287 chr4 87952173 0.21 3.185E-16 cg25444386 chr4 55990944 0.25 1.714E-18 cgl9466563 chr4 88450506 0.22 2.639E-22 cg02786012 chr4 57371589 0.26 3.964E-16 cgl5552249 chr4 88450824 0.22 7.294E-21 cg06922635 chr4 57371607 0.29 5.897E-16 cg06632027 chr4 90757378 0.30 5.198E-17 cgl5846316 chr4 57371719 0.29 1.423E-17 cg20003494 chr4 90757398 0.31 5.838E-17 cg04528060 chr4 57371868 0.37 4.383E-15 cgl4346243 chr4 90757452 0.26 1.05E-16 cg07846311 chr4 57371927 0.25 4.286E-18 cgl3549845 chr4 93225960 0.21 2.935E-16 cgl4775423 chr4 57372356 0.30 1.38E-21 cgl5076145 chr4 94748686 0.21 1.507E-17 cgll482719 chr4 57372411 0.27 7.315E-25 cg26311734 chr4 94755520 0.21 2.644E-16 cg07664553 chr4 57372597 0.31 1.95E-18 cg02853616 chr4 94755787 0.20 7.605E-16 cg21899596 chr4 57522493 0.32 1.627E-19 cg08979352 chr4 99580530 0.26 2.203E-17 cg24852548 chr4 57522632 0.32 1.291E-19 cg08663159 chr4 101111872 0.32 7.87E-18 cgl4196225 chr4 57522762 0.21 4.484E-18 cg05319305 chr4 101111927 0.26 2.058E-18 cg27305383 chr4 57522795 0.24 4.067E-18 cg25071651 chr4 101112317 0.22 5.398E-19 cgl2111309 chr4 57624039 0.22 2.146E-21 cgl2109838 chr4 103996978 0.22 4.054E-21 cg06815411 chr4 57737651 0.22 1.671E-18 cg08924430 chr4 106067052 0.30 2.508E-21 cgl9045644 chr4 57976756 0.25 1.679E-15 cgl6642281 chr4 109034555 0.25 9.59E-21 cgl5106030 chr4 74528435 -0.22 5.509E-24 cgl2938003 chr4 109092724 0.21 2.453E-15 cg22670329 chr4 74702075 0.20 2.058E-20 cgl3775316 chr4 109093218 0.23 8.116E-15 cgl9170015 chr4 74734714 0.22 1.78E-18 cg03946923 chr4 109093221 0.23 3.231E-16 cg08161323 chr4 74734762 0.25 6.165E-17 cg24071582 chr4 113430656 0.22 1.003E-14 cg02029926 chr4 74734874 0.24 5.908E-19 cg02397768 chr4 113430989 0.22 8.175E-16 cgll930554 chr4 74809912 0.33 1.997E-16 cgl7125267 chr4 115520931 0.21 6.493E-20 cg22725685 chr4 74810310 0.30 4.083E-17 cg21399832 chr4 117847410 0.25 2.695E-16 cgl3215970 chr4 74864596 0.23 5.596E-20 cgl3541713 chr4 119947251 0.22 8.051E-19 cgl6055869 chr4 74864612 0.21 6.667E-20 cg03509106 chr4 121992261 0.21 2.798E-20 cg06312813 chr4 74964493 0.23 4.648E-18 cg07492240 chr4 121994123 0.25 1.193E-24 cg03671075 chr4 78573680 0.20 1.752E-15 cg05604079 chr4 122302268 0.23 3.899E-17 cgl0752158 chr4 81185022 0.24 1.168E-20 cg02614217 chr4 122632774 0.24 5.751E-21 cg04401986 chr4 81189927 0.22 5.819E-15 cg03248158 chr4 122632918 0.32 2.878E-19 cgl6173191 chr4 82135607 0.26 1.802E-21 cg21550024 chr4 123747533 0.21 4.356E-17 cg09031823 chr4 83674996 0.24 6.141E-23 cgl7214107 chr4 123747542 0.22 1.157E-21 cg08030987 chr4 83675202 0.21 1.604E-20 cgl5128226 chr4 123747672 0.28 1.067E-21 cg08440556 chr4 83718952 0.32 3.973E-22 cg05106770 chr4 128545193 0.21 2.325E-19

_

cg24312680 chr4 128704518 0.26 3.449E-16 cgl5718581 chr4 188916581 0.26 1.535E-14 cg00224083 chr4 139773135 0.29 2.562E-27 cg00663077 chr4 188916709 0.26 2.505E-16 cgll537946 chr4 139773369 0.21 3.397E-24 cgl4817655 chr4 188916724 0.26 1.896E-17 cg06329684 chr4 140187743 0.22 1.108E-17 cg24896649 chr4 188916726 0.26 2.913E-17 cg05924540 chr4 140200723 0.28 3.78E-19 cgl8034737 chr4 188916865 0.24 9.453E-16 cg07776847 chr4 140201065 0.22 1.77E-17 cg06274159 chr4 188916867 0.24 1.286E-15 cg01733638 chr4 140201100 0.21 3.773E-17 cgl0242602 chr4 188916875 0.22 2.148E-15 cg00875805 chr4 140656749 0.23 6.88E-15 cgl4189571 chr4 188916943 0.22 3.623E-18 cg00321234 chr4 141217605 0.20 3.948E-22 cgl9858576 chr5 191806 0.22 9.457E-22 cg02628823 chr4 141419587 0.20 5.14E-14 cg06802630 chr5 322735 0.21 3.617E-17 cg01283834 chr4 141488964 0.30 5.128E-19 cg03604011 chr5 400201 0.30 4.853E-15 cg26004759 chr4 141489018 0.27 1.016E-18 cg24115232 chr5 1243907 0.26 7.164E-17 cg05644921 chr4 141489114 0.31 1.042E-20 cgl7306747 chr5 1446165 0.24 1.959E-21 cgl9876092 chr4 144208277 0.21 6.583E-19 cgl4502484 chr5 1446208 0.36 5.096E-17 cg26621699 chr4 145566903 0.21 1.15E-18 cgl6703956 chr5 1446217 0.34 1.099E-19 cgl6887264 chr4 147561775 0.20 3.493E-17 cgl3202751 chr5 1446443 0.23 2.459E-20 cg05102394 chr4 148402899 0.26 1.696E-22 cgl6498913 chr5 1851563 0.27 9.65E-20 cgll239720 chr4 152967415 0.21 9.135E-17 cg09736669 chr5 1851828 0.26 2.599E-18 cgl5410675 chr4 154144800 0.33 5.099E-21 cg25378916 chr5 1875013 0.22 8.718E-16 cg03202804 chr4 154710353 0.22 1.078E-15 cg06654549 chr5 1875058 0.21 3.014E-15 cgll354906 chr4 154710371 0.21 9.688E-18 cgl7629929 chr5 1875548 0.29 1.17E-18 cg25775322 chr4 154710373 0.22 4.945E-16 cgl8856388 chr5 1875886 0.30 3.742E-18 cg22178613 chr4 154710499 0.26 2.178E-21 cgl4564616 chr5 1876337 0.21 1.914E-15 cg05961809 chr4 154710523 0.24 5.269E-21 cg06060135 chr5 3596704 0.31 5.096E-19 cg23207990 chr4 154710535 0.23 1.168E-19 cg07881405 chr5 3597487 0.22 8.666E-16 cg00082664 chr4 154710796 0.24 4.039E-16 cg21088420 chr5 7849836 0.24 9.612E-24 cg00730887 chr4 160149604 0.20 1.205E-18 cg25214789 chr5 7850070 0.33 9.56E-21 cgl7310600 chr4 165305334 0.21 1.385E-20 cgl2539796 chr5 7850203 0.46 6.187E-23 cg09571713 chr4 168154775 0.21 2.573E-18 cg01759761 chr5 7850327 0.28 3.627E-21 cg27640794 chr4 169555699 0.21 6.941E-17 cg02602541 chr5 7850438 0.25 3.245E-15 cgl2768523 chr4 169737224 0.24 2.77E-22 cg04555220 chr5 9546695 0.25 1.154E-17 cg25054754 chr4 169754328 0.27 1.241E-18 cg03702236 chr5 9546755 0.31 2.327E-18 cgl3573928 chr4 169754534 0.26 5.77E-22 cg04096619 chr5 9547595 0.28 1.218E-23 cgl5948536 chr4 169770092 0.22 3.584E-19 cgl8334392 chr5 9547825 0.28 3.32E-24 cg24530432 chr4 174428060 0.26 6.766E-18 cg01799653 chr5 10563501 0.26 2.897E-19 cgl6509851 chr4 174430614 0.26 1.661E-18 cg22560979 chr5 10565263 0.25 1.681E-18 cgl9777067 chr4 174440103 0.24 2.274E-19 cg01937840 chr5 11588971 0.23 1.019E-22 cgl5707093 chr4 174450353 0.22 2.35E-19 cg06612088 chr5 11589016 0.26 6.768E-23 cg06609094 chr4 175132842 0.22 7.563E-15 cgl7415451 chr5 11589049 0.24 1.878E-21 cg00918522 chr4 175132871 0.23 3.1E-19 cgl6107470 chr5 12865512 -0.21 1.117E-21 cg24472939 chr4 175139486 0.27 6.152E-19 cg21215929 chr5 14873039 0.22 3.732E-21 cg07240834 chr4 175139755 0.20 1.063E-17 cg23041295 chr5 15502456 0.24 1.017E-21 cg06936231 chr4 176626819 0.20 1.014E-18 cg25623727 chr5 15932416 0.21 3.615E-24 cg03867465 chr4 183062301 0.22 4.081E-18 cgl7630392 chr5 32712623 0.20 3.601E-15 cgl5590989 chr4 183062460 0.21 1.107E-15 cg00155526 chr5 32713290 0.27 9.018E-18 cg08985979 chr4 183062576 0.21 8.78E-19 cg00266286 chr5 32713723 0.24 2.813E-16 cg02348751 chr4 183064035 0.36 3.816E-16 cg26573704 chr5 33892223 0.36 5.255E-17 cg05388880 chr4 183807081 0.22 9.025E-22 cg04124352 chr5 33892429 0.22 2.084E-16 cg01908462 chr4 184718215 0.30 7.33E-22 cgl9897071 chr5 35991382 0.22 4.948E-16 cg00966099 chr4 184718401 0.21 4.975E-14 cg26294995 chr5 36067091 0.24 1.236E-16 cg07394914 chr4 185371335 0.22 1.383E-23 cg07254421 chr5 36657993 0.20 1.082E-19 cgl5756227 chr4 185937405 0.21 1.712E-18 cgl5182643 chr5 38257516 0.26 1.282E-23 cg04006323 chr4 185937730 0.32 2.315E-25 cg03205103 chr5 38257541 0.29 2.706E-24 cgl6331929 chr4 185937863 0.24 1.704E-22 cg07833019 chr5 38258007 0.21 5.257E-16 cgl3662569 chr4 186577902 0.26 1.157E-23 cgl6317273 chr5 38258028 0.33 2.103E-23

cg22473846 chr5 38846743 0.22 4.803 E-22 cg08893692 chr5 72595741 0.22 9.933E-16 cg26597539 chr5 40680670 0.22 7.541E-16 cg22120063 chr5 72596188 0.22 8.923E-15 cg05971966 chr5 40681137 0.32 6.744E-17 cgll795854 chr5 72598965 0.28 5.555E-16 cgl3930261 chr5 42949882 0.20 8.518E-16 cg09142313 chr5 72677859 0.22 2.673E-19 cg21587238 chr5 42953590 0.24 1.845E-17 cg00177388 chr5 72677886 0.22 1.724E-20 cgl4979301 chr5 42994123 0.24 2.224E-16 cg21046148 chr5 72731905 0.24 4.289E-15 cg23502772 chr5 43191975 0.28 3.873E-21 cgl9092317 chr5 72739768 0.21 1.584E-15 cg21098557 chr5 43191993 0.27 6.393E-20 cgl5132565 chr5 72740154 0.29 8.316E-18 cgl0641714 chr5 43193681 0.30 6.741E-18 cgl8063312 chr5 72740737 0.24 4.298E-17 cg26233374 chr5 43603643 0.26 1.58E-14 cg01264639 chr5 73839484 0.21 2.669E-20 cg09489281 chr5 43604149 0.42 8.188E-16 cg07222505 chr5 74161231 0.26 5.608E-15 cgl8273840 chr5 45695643 0.23 1.8E-16 cg27379109 chr5 74907287 0.23 2.595E-17 cg23506042 chr5 50262673 0.22 3.128E-19 cg08253296 chr5 74907592 0.26 2.575E-18 cgl8063495 chr5 50262796 0.21 4.87E-14 cg07671805 chr5 74907694 0.31 4.392E-19 cg04184143 chr5 50263500 0.23 4.389E-17 cgl7555825 chr5 76924190 0.22 1.771E-19 cgll216064 chr5 50263586 0.25 1.422E-16 cg23068621 chr5 77139964 0.23 5.988E-19 cg03847373 chr5 50265767 0.27 1.699E-19 cgl7854454 chr5 77140243 0.23 3E-17 cgl8716076 chr5 50677808 0.21 1.353E-14 cgl7936721 chr5 77140543 0.24 7.856E-17 cg06875227 chr5 50683378 0.21 1.008E-18 cgl8697632 chr5 77140985 0.23 9.74E-18 cg04582364 chr5 52778441 0.24 6.259E-16 cg25051331 chr5 77253833 0.20 6.122E-22 cg27372920 chr5 52778745 0.25 5.84E-15 cg09048251 chr5 77253974 0.33 8.082E-19 cgl0932018 chr5 54516487 0.31 2.811E-15 cg07595776 chr5 77253990 0.24 2.828E-19 cg08350776 chr5 54516538 0.25 5.696E-18 cg04468543 chr5 77268331 0.21 1.857E-17 cg24828151 chr5 54516779 0.26 6.689E-17 cg04502985 chr5 77268452 0.27 1.286E-14 cgl8456523 chr5 54516805 0.34 8.249E-15 cgl3031251 chr5 77268734 0.20 8.324E-19 cgl4608384 chr5 54516879 0.21 1.705E-15 cg05907933 chr5 77268888 0.22 8.749E-17 cg26251325 chr5 54518745 0.22 2.188E-17 cg04078410 chr5 77269250 0.24 2.072E-20 cgl5384589 chr5 54873393 0.21 1.926E-23 cg05937292 chr5 77269342 0.22 5.461E-21 cg05603546 chr5 55117874 0.24 1.788E-15 cg01856645 chr5 78365647 0.22 2.019E-20 cglll82518 chr5 55117965 0.24 2.315E-15 cg06501366 chr5 78365687 0.22 5.965E-18 cgl7633020 chr5 58335180 0.30 4.477E-14 cg08328513 chr5 78365691 0.23 2.074E-17 cgl8242030 chr5 58335271 0.24 1.984E-16 cg05890484 chr5 78407552 0.20 7.337E-20 cgl7010100 chr5 59188112 0.23 1.399E-20 cg23514016 chr5 78407564 0.23 1.317E-17 cg06469229 chr5 59188213 0.22 4.774E-18 cg02286091 chr5 78407678 0.27 1.698E-18 cg03154690 chr5 59188920 0.20 5.801E-19 cgl0660256 chr5 78407683 0.23 1.887E-19 cg03323696 chr5 59189120 0.33 3.916E-19 cgll770080 chr5 78408179 0.33 1.49E-21 cg04569837 chr5 60921535 0.28 8.672E-16 cgl8058747 chr5 78408253 0.22 1.344E-18 cg08743812 chr5 71014736 0.25 8.266E-18 cgl7785773 chr5 78408347 0.22 2.968E-25 cg08351336 chr5 71014820 0.23 7.864E-23 cg00795341 chr5 79330929 0.33 6.516E-20 cg26371061 chr5 71014857 0.30 1.822E-22 cgl0784386 chr5 79330943 0.23 1.342E-19 cg01187920 chr5 71015162 0.27 5.286E-23 cgl8110483 chr5 79330959 0.26 1.517E-19 cg23300372 chr5 71015432 0.26 1.515E-14 cg03336086 chr5 79331047 0.21 3.601E-20 cg06018401 chr5 71404897 0.22 9.135E-16 cg01194371 chr5 79331477 0.21 7.202E-19 cgll018604 chr5 71507163 0.20 1.948E-21 cg01277506 chr5 80690205 0.27 1.447E-20 cgl4661148 chr5 71852862 0.23 1.093E-14 cgl7741014 chr5 80690220 0.25 2.561E-19 cgl7438030 chr5 72526379 0.21 1.615E-18 cg21942082 chr5 80690225 0.22 1.98E-18 cg07431286 chr5 72526496 0.28 3.876E-17 cg24832985 chr5 81148310 0.23 8.121E-21 cg01240795 chr5 72528314 0.20 4.955E-18 cg07201620 chr5 83679941 0.25 1.019E-16 cg22855900 chr5 72529662 0.32 3.314E-20 cg04112211 chr5 87436327 0.23 3.654E-22 cg04728482 chr5 72529902 0.29 1.284E-19 cg26081841 chr5 87441969 0.21 1.255E-17 cg02319354 chr5 72530186 0.23 1.916E-19 cgl8358723 chr5 87955618 0.20 3.747E-21 cg01141339 chr5 72530198 0.23 1.848E-21 cgl4636534 chr5 87968528 0.22 1.841E-16 cg23517208 chr5 72530472 0.22 2.09E-18 cgl2393318 chr5 87981068 0.23 2.467E-20 cgl2143789 chr5 72594461 0.21 5.43E-15 cg08850461 chr5 87990082 0.22 3.813E-17 cgl2505170 chr5 72595685 0.23 1.92E-18 cg01764252 chr5 87991071 0.21 1.357E-16

cg07533422 chr5 92935283 0.21 7.998E-18 cgl5951557 chr5 137610421 0.28 1.715E-14 cg06820621 chr5 92938232 0.21 3.797E-18 cg03721195 chr5 137610448 0.21 3.438E-15 cg27090062 chr5 92939842 0.25 1.535E-18 cg23255964 chr5 138862353 0.24 3.773E-18 cgl4615784 chr5 94955756 0.30 6.762E-15 cgl9628988 chr5 139040928 0.22 2.315E-15 cgl2864597 chr5 94955789 0.23 1.066E-14 cgl3084536 chr5 139076824 0.22 1.015E-16 cg00637687 chr5 95768915 0.21 3.464E-18 cg04600466 chr5 139076830 0.22 7.048E-17 cgl9788741 chr5 101632310 0.29 5.748E-20 cg24030507 chr5 139089274 0.28 3.699E-19 cg22149516 chr5 101632314 0.23 2.854E-20 cg01167755 chr5 139284498 0.25 8.396E-22 cg06480736 chr5 101632321 0.23 1.264E-19 cg04636402 chr5 139284774 0.21 4.722E-20 cgll267955 chr5 101632327 0.27 1.597E-18 cg22659676 chr5 139525919 0.23 1.934E-19 cg04621020 chr5 101632341 0.21 1.919E-18 cgl3887205 chr5 139525946 0.26 1.71E-20 cg08571859 chr5 112073350 0.25 3.084 E- 14 cgl2396306 chr5 140602851 0.23 4.088E-18 cg20311501 chr5 112073502 0.30 2.877E-14 cg08536529 chr5 140602889 0.21 1.336E-16 cg21634602 chr5 112073570 0.29 2.289E-15 cgl8661205 chr5 140613884 0.21 3.754E-14 cg07249274 chr5 112629565 0.33 1.412E-20 cgl7514558 chr5 140621375 0.30 4.645E-21 cgll606461 chr5 112629604 0.33 2.054E-20 cgl8664869 chr5 140625004 0.24 5.222E-19 cg08533773 chr5 113392004 0.24 1.053E-20 cg05845376 chr5 140683632 0.21 1.383E-14 cgl6707405 chr5 115152413 0.21 2.232E-15 cg07496545 chr5 140683737 0.20 3.422E-15 cg02792792 chr5 115152420 0.27 1.908E-17 cgl8781988 chr5 140723549 0.22 1.332E-15 cgl4470895 chr5 115152431 0.20 1.083E-17 cg06615730 chr5 140739877 0.21 2.631E-15 cg23180938 chr5 115152485 0.36 2.739E-19 cgl5672768 chr5 140741220 0.25 3.446E-18 cg08516516 chr5 115152492 0.28 1.495E-18 cgl3307880 chr5 140744367 0.21 5.814E-17 cgll036833 chr5 115152494 0.30 2.435E-16 cg02022808 chr5 140744914 0.24 8.348E-23 cg22010052 chr5 115298704 0.20 1.953E-16 cg02575448 chr5 140749735 0.25 2.231E-19 cg09868780 chr5 115299071 0.23 5.754E-20 cg04242499 chr5 140749745 0.23 1.765E-19 cg20403557 chr5 115299088 0.22 1.448E-20 cg26337998 chr5 140749783 0.26 4.197E-21 cgl8637698 chr5 121647154 0.20 3.519E-16 cg23348764 chr5 140749834 0.25 2.981E-20 cg04747322 chr5 121647308 0.23 7.329E-19 cg22737624 chr5 140750111 0.24 3.586E-21 cgl7807172 chr5 122620929 0.23 9.102E-19 cg09066326 chr5 140753415 0.23 1.064E-16 cg05692123 chr5 122620950 0.22 3.203E-19 cg03835609 chr5 140753418 0.23 3.42E-18 cg23949389 chr5 122621186 0.20 1.667E-20 cg26843711 chr5 140753449 0.21 1.797E-17 cgl6483725 chr5 122621240 0.29 2.453E-21 cg04637478 chr5 140753655 0.22 1.158E-20 cg05221748 chr5 122621289 0.23 1.13E-18 cg26811372 chr5 140772182 0.21 1.054E-21 cg23155911 chr5 126205009 0.31 9.051E-25 cgl4458068 chr5 140772256 0.21 6.341E-18 cg25568066 chr5 126205045 0.29 7.461E-24 cg21117330 chr5 140772286 0.20 2.848E-19 cg06918474 chr5 126205081 0.35 3.284E-22 cg24172509 chr5 140778424 0.23 7.035E-18 cg23213887 chr5 127872767 0.21 9.673E-15 cgll014124 chr5 140782297 0.25 2.846E-20 cg05686497 chr5 127874587 0.22 5.812E-17 cg00048743 chr5 140782367 0.22 3.024E-15 cg27223047 chr5 127874825 0.32 2.804 E- 20 cgl8617005 chr5 140787504 0.31 1.478E-19 cg21815063 chr5 131800430 0.21 3.9E-23 cgl8507379 chr5 140787507 0.30 3.94E-18 cgl8394340 chr5 134735613 0.24 8.654E-23 cgl3933262 chr5 140797172 0.22 5.325E-17 cgl5613420 chr5 134735637 0.27 2.248E-20 cgl4011639 chr5 140797234 0.22 4.876E-16 cg24628744 chr5 134735654 0.21 1.462E-21 cg02707176 chr5 140798758 0.27 9.064E-18 cg07458308 chr5 134827512 0.22 5.121E-16 cg05870739 chr5 140800586 0.20 5.442E-18 cg21233688 chr5 134880353 0.26 1.914E-17 cg24954895 chr5 140800761 0.21 1.211E-18 cg01821923 chr5 134914371 0.21 1.259E-17 cg21929183 chr5 140807225 0.25 1.738E-15 cgl8995088 chr5 134914734 0.27 1.705E-17 cg23082339 chr5 140810051 0.22 8.988E-24 cg03215422 chr5 135266509 0.21 1.07E-16 cg21627409 chr5 140810106 0.29 6.387E-23 cg23625660 chr5 135266516 0.22 4.807E-19 cg02452944 chr5 140810109 0.25 2.69E-22 cgl9670286 chr5 137610127 0.29 1.871E-16 cgl2304520 chr5 140810123 0.27 1.543E-23 cg02288341 chr5 137610226 0.30 8.527E-16 cg07730329 chr5 140810137 0.22 9.601E-23 cg23511432 chr5 137610255 0.35 5.561E-16 cgll647681 chr5 140810161 0.21 5.081E-21 cgl8442524 chr5 137610372 0.30 6.167E-15 cg02267483 chr5 140810404 0.20 2.73E-22 cg21225170 chr5 137610391 0.28 5.467E-15 cg21185686 chr5 140810433 0.26 6.721E-22 cg09350274 chr5 137610396 0.32 3.208E-15 cg22151446 chr5 140810805 0.29 1.432E-23 Meth.

probe ID Chr. Position P-value probe ID Chr. Position P-value

Diff. _ Diff.

cg09639151 chr5 140810920 0.30 3.992E-20 cg23483765 chr5 156886996 0.27 7.305E-15 cg23244790 chr5 140811102 0.31 2.128E-23 cg00594129 chr5 158524270 0.22 1.873E-14 cg07489502 chr5 140811642 0.34 7.917E-21 cg04248271 chr5 158524404 0.25 1.06E-15 cg26890354 chr5 140864020 0.21 1.262E-22 cg07810726 chr5 158524649 0.27 4.86E-16 cg06428620 chr5 140864276 0.36 4.693 E-26 cg06687640 chr5 159560692 0.23 9.689E-20 cgl2648074 chr5 140864474 0.26 2.135E-28 cg02384967 chr5 159738801 0.28 5.288E-23 cgl5949044 chr5 140864549 0.29 1.994E-26 cgll444704 chr5 159738916 0.36 2.682E-19 cg02022733 chr5 140864578 0.25 2.147E-29 cg26597242 chr5 161274540 0.22 1.437E-17 cg03640756 chr5 140864593 0.23 2.23E-26 cg26624398 chr5 168726889 0.23 2.813E-17 cgl5361590 chr5 140864701 0.22 2.013E-21 cg21771173 chr5 169064071 0.21 6.789E-18 cg23445461 chr5 140864733 0.30 1.217E-22 cg08862890 chr5 169064451 0.39 9.829E-21 cgl2145907 chr5 140864834 0.24 3.742E-23 cg23338503 chr5 169064530 0.28 1.843E-20 cg05494467 chr5 140892308 0.21 5.552E-15 cg05787556 chr5 170735186 0.22 4.256E-22 cg00076195 chr5 140892677 0.36 1.072E-17 cg26517714 chr5 170736245 0.21 5.891E-17 cg08860070 chr5 140892822 0.41 2.562E-18 cg26844246 chr5 170736277 0.26 7.06E-20 cg00987031 chr5 140893101 0.31 3.275E-19 cg25720804 chr5 170736389 0.24 9.86E-15 cg24137543 chr5 140893634 0.23 1.929E-19 cg06008926 chr5 170740673 0.20 1.038E-14 cg01238435 chr5 141595696 0.26 2.959E-19 cg25950112 chr5 170740870 0.28 2.228E-19 cgl8233416 chr5 141705411 0.25 1.177E-15 cg07100000 chr5 170877840 0.21 4.255E-25 cg24393055 chr5 141705521 0.25 6.12E-20 cg02125316 chr5 170878209 0.27 7.463E-21 cgl4619259 chr5 141705539 0.37 1.299E-23 cgl3656752 chr5 171538334 0.21 1.999E-16 cg05781504 chr5 145713607 0.24 1.013E-16 cg01753263 chr5 171879957 0.21 1.137E-24 cgl8274480 chr5 145713863 0.23 5.564E-17 cg05168015 chr5 171880461 0.28 1.181E-26 cgll334165 chr5 145758782 0.21 7.648E-22 cgl7777432 chr5 172068999 0.22 7.812E-18 cg08352755 chr5 145758879 0.21 1.148E-20 cg22111078 chr5 172655925 0.22 2.582E-16 cg23941434 chr5 147162161 0.24 1.39E-18 cgl9423543 chr5 172655948 0.25 1.418E-17 cg23132268 chr5 147162169 0.25 1.104E-18 cg02750098 chr5 172656021 0.20 6.757E-21 cg01965939 chr5 148442694 0.21 6.455E-19 cg26305817 chr5 172656055 0.24 6.231E-18 cg26474043 chr5 148442857 0.23 7.966E-21 cgl5929797 chr5 172660796 0.33 2.194E-21 cgl9437285 chr5 148650972 0.25 7.666E-26 cg02051616 chr5 172661132 0.20 2.266E-20 cg09651145 chr5 148651144 0.32 2.69E-22 cgl3570101 chr5 172661859 0.25 1.35E-23 cgl6429070 chr5 149535646 0.30 5.155E-25 cg08814105 chr5 172662130 0.21 4.802E-16 cg25110734 chr5 149535650 0.29 9.726E-25 cgl7842959 chr5 172664285 0.21 3.276E-19 cgl2727795 chr5 149535695 0.27 2.986E-24 cg09143673 chr5 172664439 0.25 8.191E-20 cgl2611243 chr5 149897230 0.21 4.827E-20 cgl8530551 chr5 172670879 0.25 2.627E-19 cgl9984911 chr5 150020338 0.21 1.328E-18 cgl2544191 chr5 172671754 0.21 1.107E-17 cg09501687 chr5 150169781 0.20 5.201E-18 cg23967544 chr5 172672684 0.25 8.276E-22 cgl7861277 chr5 150385659 0.20 3.228E-19 cgl7543488 chr5 172672959 0.21 1.617E-17 cgl3081720 chr5 150399890 0.25 3.593E-19 cg08506654 chr5 172673098 0.21 3.83E-20 cg21623671 chr5 150536851 0.22 4.623E-21 cg26605683 chr5 172751269 0.22 1.025E-19 cg08331313 chr5 151066460 0.24 5.639E-25 cg05469346 chr5 174115696 0.21 5.333E-16 cg25587069 chr5 151066484 0.33 1.117E-23 cg05672912 chr5 174115735 0.22 1.414E-19 cg08879559 chr5 151066486 0.30 1.108E-24 cg09491410 chr5 174178884 0.25 2.112E-15 cg23146663 chr5 151066662 0.29 2.552E-24 cg00008488 chr5 175199915 0.21 1.345E-16 cg25913233 chr5 151066683 0.26 2.06E-26 cgl2467264 chr5 175200071 0.31 1.159E-15 cg22116670 chr5 151066730 0.28 3.325E-24 cgl5622912 chr5 175225021 0.21 8.239E-22 cgl6257051 chr5 153862183 0.22 2.634E-15 cg07352345 chr5 175793049 0.22 2.822E-14 cg05212464 chr5 154071076 0.22 1.754E-20 cgl8401367 chr5 176107201 0.26 1.497E-18 cg26655340 chr5 154230141 0.27 1.067E-24 cg02460251 chr5 176107427 0.26 1.886E-18 cg00604840 chr5 154230173 0.33 1.245E-23 cglll39090 chr5 176294068 0.26 1.595E-20 cgl8188717 chr5 154230223 0.35 1.547E-23 cg08369368 chr5 176559881 0.28 2.05E-17 cgl0257049 chr5 154230308 0.30 8.515E-23 cg06183338 chr5 178004204 0.22 5.743E-17 cgl8260397 chr5 154230438 0.32 3.084E-23 cgl2483476 chr5 178421711 0.20 2.31E-14 cgl3941669 chr5 156886982 0.21 1.112E-16 cg00582971 chr5 178422128 0.24 7.679E-16 cg25090510 chr5 156886990 0.23 2.564E-15 cg22510376 chr5 178957930 0.31 2.528E-17 Meth.

probe ID Chr. Position P-value probe ID Chr. Position P-value

Diff. _ Diff.

cgl6361890 chr5 179220545 0.22 3.123E-24 cg21080336 chr6 10426657 0.25 9.032E-21 cg09629657 chr5 179220795 0.23 1.457E-28 cgl2242450 chr6 10555808 0.23 4.066E-20 cgl2200124 chr5 179220820 0.23 2.731E-23 cg05452406 chr6 10881891 0.33 7.576E-19 cgl9759135 chr5 179221059 0.30 2.245E-24 cg09516476 chr6 10881925 0.26 2.401E-21 cgl5126957 chr5 179246594 0.21 2.63E-16 cg22851295 chr6 10881949 0.22 9.028E-19 cgl2408990 chr5 179634671 0.29 4.424E-21 cg02844545 chr6 10882043 0.24 2.998E-18 cgl9978312 chr5 179634688 0.27 3.344E-19 cg09829319 chr6 10882238 0.26 1.452E-17 cgl8652367 chr5 180017689 0.24 2.395E-19 cgl4250833 chr6 10882240 0.36 3.797E-17 cg07317366 chr5 180017846 0.24 2.298E-23 cg20229534 chr6 10882250 0.35 6.32E-18 cg21919857 chr5 180018102 0.35 3.258E-22 cg24329557 chr6 10882326 0.24 1.867E-20 cgl9897330 chr5 180018201 0.35 1.016E-23 cgl4000361 chr6 10882336 0.39 3.141E-21 cg09500443 chr5 180018465 0.24 8.276E-18 cgl7991695 chr6 10882974 0.26 8.012E-22 cg22859061 chr5 180018503 0.32 1.731E-18 cgl5244049 chr6 10883376 0.28 8.529E-22 cg01934626 chr5 180018562 0.33 5.146E-18 cgll796455 chr6 10883895 0.25 2.055E-21 cgll916729 chr5 180018564 0.31 1.728E-18 cg09775263 chr6 10884094 0.25 9.008E-20 cg06732395 chr5 180018722 0.24 6.994E-21 cg24113409 chr6 10884314 0.22 1.078E-20 cgl7403609 chr5 180075862 0.35 2.713E-21 cg23233404 chr6 10887587 0.24 2.36E-14 cg00489401 chr5 180075875 0.32 1.379E-21 cgl3246235 chr6 12749978 0.20 1.389E-14 cg08368654 chr6 1378868 0.25 4.582E-16 cgl3699887 chr6 16320488 0.27 5.622E-16 cg21347053 chr6 1624978 0.25 4.882E-17 cgll228682 chr6 16320530 0.34 1.148E-15 cg20384898 chr6 1625111 0.27 1.444E-20 cg05085500 chr6 19692172 0.26 6.357E-17 cg08513472 chr6 1625238 0.30 7.131E-18 cg01866955 chr6 19692217 0.23 1.634E-16 cg06080793 chr6 1625457 0.25 2.611E-19 cgl4151259 chr6 19837015 0.21 1.481E-17 cg04497116 chr6 1625574 0.32 3.394E-20 cg23165899 chr6 19837095 0.21 4.538E-18 cg25003777 chr6 2841626 0.28 5.346E-22 cg06213964 chr6 21665905 0.23 7.445E-16 cg07635623 chr6 2841875 0.34 2.904E-17 cgll900861 chr6 21666666 0.23 2.89E-15 cgl5199326 chr6 2842005 0.22 1.314E-19 cg00641409 chr6 21666778 0.23 1.871E-15 cgl9349369 chr6 2842146 0.26 5.876E-16 cgl2347429 chr6 21666834 0.25 1.95E-15 cgl4652638 chr6 2842215 0.24 1.213E-17 cg26158950 chr6 21667166 0.24 7.992E-24 cg27056119 chr6 2842239 0.30 1.592E-15 cg08233811 chr6 21667333 0.25 2.236E-25 cg08542865 chr6 2842248 0.30 7.347E-17 cg06341027 chr6 21667407 0.23 1.048E-24 cg00031256 chr6 2842255 0.27 1.519E-15 cgl5140902 chr6 21667815 0.31 9.737E-26 cgl7298973 chr6 2876494 0.23 5.352E-17 cgl0126181 chr6 21832051 0.22 1.636E-23 cgl8676237 chr6 2903258 0.21 4.636E-15 cg03854238 chr6 22071933 0.28 3.621E-26 cgl3722431 chr6 2903533 0.27 2.027E-16 cg08818610 chr6 24910720 0.23 3.944E-15 cg07182669 chr6 2903535 0.25 6.595E-15 cg04682791 chr6 25313030 0.21 2.657E-20 cg07844977 chr6 2903699 0.25 1.254E-18 cg07816556 chr6 26017280 0.23 1.022E-16 cg22336806 chr6 2903704 0.25 3.349E-14 cg08511651 chr6 26017619 0.24 9.107E-18 cg24021113 chr6 3752849 0.22 1.843E-18 cgl0146929 chr6 26017939 0.27 1.64E-15 cgl9700787 chr6 3997547 0.20 7.824E-18 cgll282676 chr6 26018003 0.26 6.198E-16 cg02104162 chr6 4610716 0.25 1.698E-20 cgl4703002 chr6 26018058 0.28 3.502E-14 cgl8559739 chr6 4775132 0.23 6.762E-16 cg23829024 chr6 26018074 0.29 4.507E-15 cg24816460 chr6 4775203 0.34 1.099E-18 cgl5741433 chr6 26018084 0.23 3.472E-16 cg08249424 chr6 4775222 0.25 1.767E-17 cg21425842 chr6 26240939 0.24 1.285E-14 cgll935248 chr6 4942483 0.22 5.293E-22 cg02909790 chr6 26271587 0.21 3.891E-16 cg08815340 chr6 5026435 0.21 3.2E-14 cgl4273822 chr6 26271716 0.29 8.427E-17 cg21770800 chr6 5994982 0.20 4.743E-14 cg00036011 chr6 26271718 0.29 6.838E-17 cgl0304637 chr6 6003220 0.30 2.063E-16 cg01563704 chr6 26271816 0.27 7.591E-18 cgll564981 chr6 6007670 0.24 5.908E-15 cgll731890 chr6 26271827 0.28 1.26E-17 cgl6530177 chr6 6320324 0.27 5.769E-16 cg23233200 chr6 26272695 0.22 6.324E-15 cgl3809441 chr6 6737631 0.20 6.834E-19 cgl2311490 chr6 26331721 0.21 8.254E-16 cg25370658 chr6 7673306 0.21 3.898E-20 cg21674495 chr6 26331727 0.20 5.49E-15 cg07721569 chr6 10420287 0.21 3.77E-15 cgl6519587 chr6 26614649 0.22 2.231E-14 cgl6754467 chr6 10426588 0.29 1.293E-14 cglll83365 chr6 27064769 0.32 2.143E-16 cg26987855 chr6 10426637 0.28 5.715E-18 cg22058855 chr6 27064968 0.26 9.555E-18

cgl2298212 chr6 27065003 0.23 5.779E-19 cgl2287358 chr6 29796032 0.24 1.403E-16 cg03359964 chr6 27125955 0.22 1.987E-15 cgll363230 chr6 29796351 0.20 2.426E-14 cg06321998 chr6 27173991 0.22 2.691E-18 cgl3516209 chr6 29855302 0.24 1.586E-16 cg06374079 chr6 27182908 0.23 1.477E-17 cg00113675 chr6 29855347 0.27 4.104E-20 cg09513990 chr6 27235822 0.30 5.548E-17 cgl0262387 chr6 29855435 0.30 2.601E-20 cg05422029 chr6 27235843 0.28 2.353E-18 cg23130010 chr6 29855462 0.24 6.234E-22 cg01518607 chr6 27235891 0.35 2.441E-18 cg01362455 chr6 29855490 0.22 2.974E-16 cgl7605021 chr6 27247586 0.23 3.821E-20 cg01062395 chr6 29855636 0.22 4.589E-20 cg27131891 chr6 27513414 0.22 2.068E-16 cg26268701 chr6 29894737 0.28 1.745E-16 cg05310764 chr6 27513479 0.23 8.753E-18 cgl5931205 chr6 29894820 0.39 3.1E-17 cg24892966 chr6 27526023 0.26 2.535E-16 cg09746279 chr6 29895016 0.24 6.433E-18 cgl0903903 chr6 27647843 0.24 2.17E-15 cg01336390 chr6 29895059 0.25 6.135E-17 cgl4558529 chr6 27648341 0.27 1.575E-18 cg04109898 chr6 29943455 0.27 1.041E-14 cgl0799055 chr6 27725188 0.28 1.964E-22 cgl3115683 chr6 29943460 0.23 1.674E-14 cg06323023 chr6 27841352 0.22 2.012E-14 cgl7639394 chr6 29943480 0.26 4.399E-15 cgl7965019 chr6 27858545 0.26 3.686E-16 cg08879910 chr6 29974319 0.38 1.802E-17 cgl7718302 chr6 27858637 0.23 3.815E-17 cg23026024 chr6 29974512 0.31 1.108E-18 cg06470822 chr6 28175283 0.21 1.032E-20 cgl3338877 chr6 29974531 0.23 4.344E-18 cg03111404 chr6 28175984 0.25 1.062E-18 cg24725574 chr6 29974717 0.27 4.631E-21 cgl2172441 chr6 28176163 0.23 6.744E-19 cg01814945 chr6 29974723 0.21 6.906E-21 cgl8675097 chr6 28227127 0.20 8.856E-17 cg23313031 chr6 29974745 0.23 1.74E-16 cg25666433 chr6 28367279 0.25 1.105E-19 cgl9448822 chr6 29974773 0.21 3.283E-15 cg02622316 chr6 28367410 0.32 2.603E-18 cgll867546 chr6 29974810 0.26 4.013E-14 cg23164203 chr6 28367475 0.25 3.006E-17 cg23483840 chr6 29974844 0.32 1.19E-14 cg25060829 chr6 28367571 0.25 2.245E-16 cg08163199 chr6 29974858 0.40 1.546E-16 cgl8815343 chr6 28367644 0.23 1.604E-18 cg25318809 chr6 29974863 0.40 2.093E-17 cg20275132 chr6 28367749 0.23 8.188E-17 cgl4781281 chr6 29974868 0.33 2.602E-15 cgl5032142 chr6 28414780 0.20 9.099E-15 cg08325845 chr6 29974886 0.37 2.256E-17 cg09971314 chr6 28415023 0.27 2.927E-17 cgl5726260 chr6 29974900 0.30 2.921E-18 cg26418589 chr6 28442796 0.20 7.563E-17 cgl2976581 chr6 29975032 0.31 2.938E-16 cg02227292 chr6 28442848 0.21 8.154E-18 cgl4432143 chr6 29975061 0.31 2.411E-16 cg09151979 chr6 28457624 0.20 3.664E-14 cg21330423 chr6 29975068 0.37 2.489E-16 cg04650654 chr6 28505429 0.22 2.826E-17 cg09659004 chr6 29975078 0.33 5.478E-15 cg27168780 chr6 28521796 0.27 6.012E-16 cgl5364169 chr6 29975080 0.22 5.727E-17 cg05954411 chr6 28521811 0.22 2.427E-16 cgl8347921 chr6 29975366 0.22 5.826E-19 cgll445094 chr6 28521837 0.26 5.317E-16 cg25120945 chr6 29975416 0.24 3.134E-21 cg20657849 chr6 28557400 0.23 2.579E-16 cgl2034345 chr6 29975427 0.21 1.099E-19 cgl5880846 chr6 28557424 0.25 1.798E-17 cg08491487 chr6 30039130 0.21 1.559E-14 cg06866163 chr6 28557486 0.23 1.171E-15 cg06893296 chr6 30095136 0.24 6.056E-22 cgl8383538 chr6 28557823 0.21 1.237E-17 cg25247859 chr6 30095174 0.26 3.352E-20 cgl0465866 chr6 28574471 0.25 1.886E-18 cg05745631 chr6 30095178 0.28 3.243E-21 cg24643706 chr6 28603779 0.30 8.326E-19 cg05068206 chr6 30095195 0.25 3.588E-21 cgl3187764 chr6 28677521 0.22 2.646E-19 cg23079252 chr6 30095199 0.29 1.426E-22 cg24181771 chr6 28706472 0.21 2.338E-17 cg21334513 chr6 30095248 0.35 1.58E-21 cg05457768 chr6 28751790 0.21 1.145E-17 cg27282900 chr6 30095258 0.31 1.222E-22 cg24717325 chr6 28784509 0.21 7.088E-16 cg02049405 chr6 30095265 0.21 6.687E-22 cg08377819 chr6 28956268 0.23 4.577E-19 cgl8628732 chr6 30095295 0.22 1.643E-23 cg20691507 chr6 28956683 0.22 4.029E-15 cgl7034390 chr6 30095326 0.21 3.34E-21 cg20034792 chr6 29521781 0.25 6.661E-15 cg05994850 chr6 30095341 0.24 8.773E-20 cg26131286 chr6 29521783 0.24 6.895E-15 cg26719062 chr6 30095349 0.26 2.58E-22 cg26142965 chr6 29521803 0.20 1.719E-19 cgl8055610 chr6 30095419 0.21 1.757E-17 cgl5385139 chr6 29595506 0.26 2.208E-19 cgl9059495 chr6 30095495 0.30 8.5E-23 cg20927242 chr6 29692011 0.34 1.706E-14 cg01964152 chr6 30095546 0.26 1.231E-19 cg03521696 chr6 29795595 0.23 1.748E-15 cg08548396 chr6 30095549 0.27 2.99E-21 cg21529533 chr6 29796015 0.22 2.219E-16 cg01528052 chr6 30095728 0.25 8.623E-20

_

cg03771840 chr6 30140145 0.24 4.347E-19 cgl0551329 chr6 32120933 0.24 1.761E-16 cg23119604 chr6 30227854 0.23 4.39E-14 cgl6481280 chr6 32120955 0.22 1.501E-17 cgl2007166 chr6 30228058 0.21 1.016E-17 cg01111041 chr6 32121055 0.23 1.113E-18 cg07723510 chr6 30228063 0.25 6.156E-17 cg00110832 chr6 32121130 0.21 4.783E-21 cgll456756 chr6 30228069 0.29 9.105E-19 cgll386011 chr6 32121156 0.23 2.26E-19 cg27011480 chr6 30228083 0.34 2.982E-17 cgl2738718 chr6 32121204 0.25 8.511E-21 cgl8940843 chr6 30418773 0.22 2.767E-22 cgl4130039 chr6 32121225 0.29 5.407E-19 cgl8663382 chr6 30418789 0.21 2.118E-24 cg05133205 chr6 32121249 0.32 1.233E-19 cgl0110083 chr6 30418845 0.22 3.428E-25 cgl7329164 chr6 32121259 0.28 8.001E-18 cgl6019142 chr6 30418900 0.25 1.794E-27 cgl8049167 chr6 32121261 0.26 1.207E-17 cg05326023 chr6 30418908 0.25 2.389E-27 cgl2585943 chr6 32121368 0.20 5.869E-18 cg04170192 chr6 30418941 0.29 1.341E-21 cgl3102294 chr6 32121393 0.22 5.104E-18 cg07830436 chr6 30419066 0.21 1.189E-20 cg00552704 chr6 32121420 0.25 7.593E-18 cg04273431 chr6 30523215 0.21 1.771E-23 cg06264679 chr6 32121433 0.23 7.296E-17 cg21264055 chr6 30523242 0.23 6.242E-25 cg05525649 chr6 32156269 0.20 1.155E-21 cg23167351 chr6 30650737 0.22 6.606E-22 cg01738650 chr6 32223076 0.28 1.332E-22 cgl8586886 chr6 30652399 0.20 1.143E-15 cg22370379 chr6 32223090 0.25 2.604E-22 cg08794940 chr6 30711073 0.25 4.611E-18 cgl4914046 chr6 32223098 0.29 2.578E-23 cgl4433074 chr6 30711090 0.29 2.301E-21 cgll720950 chr6 32223114 0.26 3.121E-24 cgl9033654 chr6 30711138 0.32 8.644E-21 cgl0187879 chr6 32223208 0.31 1.085E-22 cg09235583 chr6 30711141 0.28 1.599E-20 cgl7990771 chr6 32223226 0.22 9.959E-22 cg04012931 chr6 30711164 0.22 3.376E-20 cgl9263700 chr6 32223236 0.31 2.444E-22 cg08687386 chr6 30711206 0.21 4.345E-20 cg09715059 chr6 32223336 0.23 2.713E-19 cg07858113 chr6 30711561 0.25 5.265E-20 cg00523604 chr6 32223341 0.23 2.26E-21 cgl2232308 chr6 30711580 0.22 3.024E-21 cgl0397527 chr6 32977217 0.29 8.176E-25 cg08457178 chr6 30711636 0.21 5.806E-19 cg26168907 chr6 32977223 0.22 9.915E-22 cgl7389738 chr6 30711642 0.21 2.666E-22 cg04809274 chr6 32977254 0.22 2.223E-21 cg27545367 chr6 30711644 0.23 3.137E-19 cg08481075 chr6 33161328 0.24 2.309E-14 cg20178172 chr6 30711655 0.20 5.612E-20 cg03512637 chr6 33215685 0.21 1.788E-22 cgl3804182 chr6 30711796 0.30 3.452E-20 cgl6231241 chr6 33215838 0.20 1.207E-16 cgl6493531 chr6 30711802 0.29 5.488E-20 cg09706021 chr6 33399109 0.22 4.815E-22 cg06126421 chr6 30720080 0.21 4.993E-21 cgl7674042 chr6 34482479 0.23 1.132E-17 cgl4753356 chr6 30720108 0.24 1.733E-22 cg25927215 chr6 34677450 0.23 1.666E-20 cgl9913563 chr6 30720261 0.24 1.154E-20 cg08194377 chr6 34984836 0.22 1.647E-22 cg03720100 chr6 30720263 0.21 4.885E-21 cg02665650 chr6 34984838 0.23 1.898E-21 cg06422467 chr6 30720484 0.25 3.302E-21 cg07207982 chr6 34984930 0.23 5.503E-20 cgl6137928 chr6 30720491 0.22 1.731E-20 cg21604042 chr6 35181401 0.22 7.01E-19 cg00474080 chr6 30923243 0.27 3.069E-21 cg00347904 chr6 35182508 0.26 3.958E-17 cgll935153 chr6 30923306 0.22 1.221E-16 cg20595752 chr6 35458416 0.24 1.775E-24 cg00179217 chr6 31831340 0.26 9.014E-23 cg26319579 chr6 35466014 0.24 5.857E-16 cg20383155 chr6 31831428 0.25 3.557E-20 cgl5219228 chr6 35479628 0.30 1.064E-18 cgl8363192 chr6 31831434 0.26 1.25E-21 cg24281267 chr6 35479648 0.25 1.207E-17 cg22753340 chr6 31831489 0.24 5.455E-21 cgl2827262 chr6 35479910 0.24 5.005E-15 cg00397479 chr6 31831510 0.28 2.547E-21 cgll764900 chr6 38683035 0.22 4.592E-18 cg27084746 chr6 31831532 0.25 8.048E-21 cg03166753 chr6 38683221 0.22 3.369E-16 cgl5632826 chr6 31831740 0.25 5.559E-23 cg01985396 chr6 39760833 0.20 7.736E-20 cg21116447 chr6 31831803 0.22 8.724E-20 cgl9653212 chr6 42145954 0.28 2.31E-16 cg06060835 chr6 31913809 0.24 2.666E-18 cgl4931854 chr6 42738967 0.34 1.244E-17 cgl3035743 chr6 32119685 0.26 2.692E-17 cg07481320 chr6 42739021 0.23 7.405E-16 cgl2602633 chr6 32119691 0.26 5.361E-18 cg24520538 chr6 42739049 0.24 1.133E-14 cg08045906 chr6 32120625 0.23 5.67E-15 cg09645574 chr6 42879382 0.26 6.19E-20 cgl2883279 chr6 32120773 0.21 3.975E-16 cg01075005 chr6 42879409 0.20 1.69E-18 cgl2626589 chr6 32120783 0.21 8.469E-16 cg27363327 chr6 43211208 0.27 6.224E-18 cg06025456 chr6 32120863 0.21 2.782E-18 cgl6620382 chr6 43211213 0.26 5.754E-17 cgl3934406 chr6 32120878 0.21 1.311E-20 cg25965471 chr6 43211235 0.20 6.888E-15

cg22970435 chr6 44310228 0.21 2.767E-23 cgl4065115 chr6 100916959 0.21 3.493E-18 cg26145959 chr6 44310257 0.22 4.148E-22 cgl6042259 chr6 100917206 0.22 3.91E-17 cgl8959554 chr6 44310345 0.28 2.837E-22 cg02391713 chr6 105400985 0.27 1.789E-17 cgl3077262 chr6 44310350 0.28 1.218E-24 cg22620090 chr6 105400993 0.29 3.685E-18 cg09662584 chr6 44310445 0.22 7.981E-24 cgl7933583 chr6 105401673 0.24 1.48E-19 cg07188523 chr6 44528793 0.27 5.339E-23 cg20624391 chr6 105584149 0.22 1.949E-17 cgl8818075 chr6 44528865 0.27 4.547E-22 cgl4765959 chr6 106429316 0.26 2.266E-15 cg01740766 chr6 44528958 0.23 3.666E-23 cg09581551 chr6 107810162 0.25 4.551E-16 cg24428325 chr6 44529081 0.27 3.413E-23 cgl5666214 chr6 108438316 0.22 6.806E-18 cgl0953487 chr6 44529157 0.23 6.108E-22 cg02134353 chr6 108440118 0.26 1.491E-19 cgll412703 chr6 44629403 0.21 8.73E-17 cg20295992 chr6 108440280 0.32 1.142E-15 cg23376821 chr6 45391365 0.26 1.007E-16 cg08382226 chr6 108440339 0.36 8.893E-22 cg25865108 chr6 45559104 0.21 4.453E-21 cg01513307 chr6 108479557 0.22 7.677E-17 cgll848487 chr6 48035985 0.20 1.245E-23 cgl4712531 chr6 108485043 0.23 3.933E-16 cg01035198 chr6 49519250 0.22 1.459E-15 cg24472375 chr6 108485102 0.21 1.247E-14 cg07103129 chr6 50787964 0.23 2.458E-17 cgl7386213 chr6 108488335 0.31 6.359E-19 cg27260772 chr6 50791202 0.34 3.819E-18 cg05135644 chr6 108489795 0.23 3.303E-20 cgl7343563 chr6 50803945 0.22 6.25E-17 cg04407470 chr6 108489977 0.32 1.433E-16 cg08178940 chr6 50808627 0.25 3.674E-17 cgl3776285 chr6 108490264 0.20 1.404E-19 cg08857063 chr6 50808667 0.21 4.814E-18 cg00170003 chr6 108490371 0.24 3.985E-19 cg09363735 chr6 50808699 0.21 4.89E-17 cgl5347342 chr6 108490485 0.21 3.554E-19 cg03159396 chr6 50808813 0.22 1.945E-17 cg25775494 chr6 108490895 0.20 1.605E-18 cg00908833 chr6 50810432 0.22 8.684E-17 cg23676151 chr6 108491372 0.22 1.126E-17 cg22282405 chr6 50810682 0.25 1.778E-15 cg20731469 chr6 108495678 0.22 2.015E-16 cg06564232 chr6 50810993 0.20 4.069E-17 cgl3784235 chr6 108495865 0.25 1.254E-19 cg05437823 chr6 50813676 0.20 2.05E-14 cg21762523 chr6 108497717 0.28 4.863E-21 cg00155310 chr6 50814011 0.24 4.616E-17 cg03673965 chr6 108497734 0.24 4.797E-20 cg21766898 chr6 50814089 0.22 2.343E-17 cg20931973 chr6 110679832 0.22 7.402E-22 cg01791371 chr6 50817193 0.24 3.66E-19 cgl4482998 chr6 111984370 0.20 2.282E-20 cgl6758813 chr6 50818862 0.21 3.546E-19 cgl5366353 chr6 116691382 0.25 1.282E-23 cg04276508 chr6 50819054 0.23 3.337E-17 cgl2708994 chr6 116691460 0.26 4.807E-21 cg07436152 chr6 50819236 0.22 4.679E-19 cg09025324 chr6 116691685 0.28 3.051E-18 cg02373152 chr6 52227767 0.39 1.53E-23 cgl8254850 chr6 116691851 0.29 3.676E-14 cgll907729 chr6 55443757 0.20 6.918E-15 cgl9869037 chr6 116732515 0.24 3.446E-24 cg06401021 chr6 55443868 0.24 1.11E-17 cg08071609 chr6 117086040 0.23 8.952E-19 cg08664487 chr6 56818409 0.20 6.843E-19 cgl0446179 chr6 121758653 0.29 1.21E-20 cg00228475 chr6 58149279 0.20 8.76E-16 cg26332253 chr6 121758729 0.27 2.112E-19 cg05211057 chr6 70992454 0.22 1.391E-15 cgl0992014 chr6 121758817 0.22 3.585E-21 cg24399122 chr6 70992907 0.20 6.871E-18 cgl7160382 chr6 121758980 0.32 8.576E-20 cg02447304 chr6 74024628 0.23 1.026E-14 cgl0182317 chr6 123317487 0.23 7.06E-17 cgl8132916 chr6 79620363 0.34 2.066E-18 cg08194879 chr6 123317569 0.21 1.531E-16 cg09184832 chr6 79620586 0.22 2.8E-15 cg01047555 chr6 127835990 0.23 2.399E-21 cgll833968 chr6 79620685 0.27 1.124E-18 cgl3612083 chr6 127836053 0.20 1.266E-21 cg24302752 chr6 80853625 0.22 4.919E-18 cgl2462816 chr6 127836107 0.29 9.806E-19 cg07335294 chr6 84417933 0.20 2.537E-18 cgl6001722 chr6 127836159 0.24 4.085E-18 cg21985590 chr6 84563910 0.20 2.142E-21 cg20640433 chr6 129204206 0.28 8.061E-18 cg08445802 chr6 85482612 0.26 3.839E-14 cg02446647 chr6 133562101 0.26 2.941E-21 cg23172664 chr6 86169204 0.23 2.326E-21 cg20286200 chr6 133562267 0.21 5.319E-16 cgl5232240 chr6 90143704 0.22 4.147E-15 cg05062333 chr6 133562269 0.21 5.19E-19 cg08747277 chr6 96048126 0.23 4.154E-20 cg01162672 chr6 133562275 0.22 5.779E-18 cg07184578 chr6 99291343 0.20 1.689E-14 cgll664500 chr6 133562479 0.26 9.334E-16 cg03244411 chr6 99295790 0.21 3.538E-18 cgl4287112 chr6 133562485 0.24 1.929E-15 cg06558014 chr6 100051116 0.24 5.054E-17 cg22871668 chr6 133562492 0.25 1.236E-15 Meth. Meth. probe ID Chr. Position P-value probe ID Chr. Position P-value

Diff. Diff.

cgl4270292 chr6 133562494 0.26 1.474E-17 cg00266983 chr7 1277521 0.28 4.142E-14 cg24176563 chr6 133562776 0.20 5.202E-16 cg06507579 chr7 1282819 0.23 6.519E-19 cg04467618 chr6 134210946 0.20 2.011E-16 cgl8090004 chr7 1283896 0.27 5.766E-20 cg26870192 chr6 137242062 0.27 7.267E-17 cg24846199 chr7 1283915 0.33 9.623E-22 cgl8141830 chr6 137242085 0.21 4.836E-17 cg00338391 chr7 1283981 0.26 4.34E-17 cg03586474 chr6 137242147 0.25 1.006E-16 cg07296447 chr7 1286023 0.22 1.151E-15 cgl0242496 chr6 137242316 0.23 4.424E-17 cg00919971 chr7 1286149 0.28 3.24E-18 cg07893921 chr6 137809124 0.22 6.894E-16 cgl6275882 chr7 1288184 0.20 3.624E-17 cgl4251870 chr6 137809529 0.29 2.908E-17 cgl6414149 chr7 1294013 0.25 1.555E-23 cg03602029 chr6 137814078 0.24 9.323E-17 cgl0418812 chr7 1850329 0.21 2.546E-19 cgl0071643 chr6 137814356 0.22 4.214E-18 cg07446753 chr7 2527391 0.21 2.912E-17 cg01972751 chr6 137814728 0.27 8.074E-16 cgl9869035 chr7 2653955 0.21 1.458E-19 cgl2744820 chr6 137814960 0.29 3.531E-19 cg25588389 chr7 2654420 0.24 4.29E-17 cgl7295225 chr6 137814971 0.25 1.015E-19 cg26551200 chr7 2681369 0.22 4.859E-21 cg01968402 chr6 137817775 0.23 1.04E-18 cgl7550566 chr7 2681436 0.22 4.63E-22 cg21730858 chr6 138806320 0.21 1.057E-20 cg24192569 chr7 4184151 0.20 4.141E-16 cg25278941 chr6 139795527 0.20 1.338E-22 cg06010020 chr7 5112067 0.23 3.223E-17 cgll640756 chr6 143247810 0.22 2.677E-20 cg20653955 chr7 6566649 0.21 2.291E-19 cgl4646893 chr6 143592425 0.21 8.95E-21 cg05732750 chr7 6704045 0.27 1.735E-17 cgl3319975 chr6 146136371 0.27 1.947E-14 cgl2597389 chr7 8482235 0.25 4.534E-17 cg23095615 chr6 146136563 0.37 4.235E-20 cg06335867 chr7 8482325 0.28 6.248E-16 cg09094393 chr6 146136749 0.35 2.882E-23 cgll825059 chr7 14876371 0.21 1.068E-24 cg08958294 chr6 146350131 0.20 2.63E-14 cg24303731 chr7 14942359 0.24 5.753E-15 cg03354508 chr6 147769498 0.20 1.566E-14 cgll417025 chr7 16505589 0.28 5.102E-22 cgll009590 chr6 149082648 0.27 1.398E-18 cg07220448 chr7 16505592 0.29 6.16E-22 cgl0308253 chr6 149803111 0.20 1.041E-16 cg06363129 chr7 16505602 0.24 1.677E-23 cgll660826 chr6 150286508 0.27 4.852E-23 cg06126713 chr7 16505617 0.29 1.995E-20 cg20134151 chr6 150463500 0.23 2.758E-18 cgl3864794 chr7 16505664 0.25 3.277E-17 cg09070799 chr6 151561236 0.22 1.416E-17 cg08146609 chr7 18535232 0.22 7.115E-19 cg27296341 chr6 154485839 0.21 1.446E-23 cgll321459 chr7 18535263 0.25 7.194E-19 cg09226986 chr6 160852328 0.21 1.989E-23 cgl9585556 chr7 18535332 0.27 1.94E-18 cg07260592 chr6 161100122 0.24 1.609E-14 cg25620356 chr7 18535407 0.24 3.53E-18 cg00991875 chr6 161100376 0.21 5.504E-16 cgl2081743 chr7 18535499 0.31 6.574E-19 cgl8825119 chr6 163149453 0.20 7.369E-20 cgll765288 chr7 18535767 0.23 1.221E-17 cg07126525 chr6 166218519 0.24 8.05E-16 cg02179455 chr7 19183732 0.21 5.042E-14 cgl9997946 chr6 166399986 0.21 3.721E-16 cg24624901 chr7 19184273 0.25 4.301E-16 cg03177042 chr6 166422671 0.20 2.567E-17 cg23536473 chr7 19184555 0.22 1.838E-14 cg20114732 chr6 166579135 0.27 1.391E-16 cgl0477621 chr7 19184950 0.23 6.225E-16 cg06463958 chr6 166582393 0.27 3.53E-15 cg25691167 chr7 19184961 0.28 1.503E-16 cg05573767 chr6 167171394 0.24 1.862E-21 cg06896909 chr7 19813297 0.21 3.394E-19 cg27537164 chr6 168079127 0.23 1.23E-17 cg04111071 chr7 19813299 0.23 6.533E-16 cg08515442 chr6 168778225 0.22 4.681E-21 cg24954668 chr7 20833585 0.26 6.875E-15 cgl0781468 chr6 168778312 0.21 4.466E-19 cg03521044 chr7 20838564 0.20 8.217E-16 cg09499136 chr6 168975608 0.21 5.9E-23 cgl3279244 chr7 20838581 0.20 2.904E-15 cg00084338 chr6 170595920 0.25 3.723E-19 cg00684125 chr7 21209165 0.28 7.564E-24 cg03120555 chr7 630473 0.24 2.055E-19 cg24803391 chr7 21209338 0.26 2.205E-24 cg23605961 chr7 751331 0.28 3.244E-18 cgl6448636 chr7 21209509 0.23 4.857E-22 cg24473500 chr7 871436 0.20 2.833E-18 cg08701183 chr7 21209781 0.22 1.585E-23 cg06145435 chr7 1022769 0.24 3.693E-19 cgl7344321 chr7 22617382 0.23 8.073E-17 cg09414673 chr7 1022797 0.22 2.16E-16 cg23991636 chr7 23507657 0.22 3.753E-18 cgl7372657 chr7 1216933 0.20 3.257E-16 cgl2935170 chr7 23508189 0.22 2.754E-16 cg01240056 chr7 1263927 0.28 3.086E-16 cg06832339 chr7 23842119 0.23 2.485E-19 cg21042456 chr7 1270558 0.27 5.884E-18 cg09333471 chr7 24796355 0.21 3.234E-20 cg23168531 chr7 1270601 0.21 3.483E-18 cgl7485838 chr7 27138712 0.25 2.652E-14 cgll213369 chr7 1270925 0.21 1.025E-17 cgl6644023 chr7 27154845 0.21 1.929E-22

cgl5982700 chr7 27154911 0.21 3.466E-19 cgl4045872 chr7 49813065 0.23 4.1E-15 cg22798849 chr7 27155234 0.21 3.806E-19 cg01893212 chr7 49813088 0.30 6.126E-19 cg23432345 chr7 27196153 0.23 1.314E-14 cg02467990 chr7 49813102 0.31 6.004E-19 cg07302069 chr7 27196286 0.43 1.34E-16 cg09493505 chr7 49813111 0.25 5.098E-16 cg20293594 chr7 27196296 0.30 1.48E-18 cgl8023455 chr7 49894664 0.22 3.658E-18 cg05471296 chr7 27196302 0.33 9.374E-21 cgl8607529 chr7 50343869 0.23 3.81E-19 cgl5797110 chr7 27196314 0.30 5.707E-20 cg07589773 chr7 50343883 0.21 1.198E-18 cg09017619 chr7 27196320 0.33 1.551E-21 cg27633530 chr7 50344294 0.20 1.791E-18 cg05743885 chr7 27196365 0.27 7.202 E-21 cg20078466 chr7 50344331 0.24 1.675E-17 cgl9153763 chr7 27196371 0.21 1.234E-19 cg07114310 chr7 51538921 0.28 7.018E-21 cgl0474350 chr7 27196555 0.24 6.564E-21 cg02897667 chr7 51539131 0.21 1.253E-18 cg08637618 chr7 27279329 0.25 1.581E-16 cgl0614809 chr7 51539190 0.27 3.15E-18 cg07702750 chr7 28998214 0.24 3.661E-14 cgl2988117 chr7 51658747 0.23 1.125E-19 cg22675801 chr7 28998346 0.26 4.491E-15 cgl8793404 chr7 52156489 0.24 1.461E-20 cg04926881 chr7 29024378 0.26 7.84E-21 cg21336434 chr7 54271282 0.20 9.108E-20 cg22187722 chr7 29185965 0.34 3.235E-17 cgl4225678 chr7 54612325 0.22 8.314E-16 cg24448259 chr7 29186110 0.22 6.531E-15 cg21179088 chr7 54612333 0.26 1.35E-19 cgll044163 chr7 29186153 0.26 1.263E-14 cg03276785 chr7 54956202 0.26 4.779E-22 cgl7052266 chr7 29186183 0.29 6.417E-16 cgl9259179 chr7 54956252 0.28 3.226E-23 cg02032778 chr7 29186228 0.29 9.407E-16 cgl3208318 chr7 54956274 0.28 5.161E-23 cgl5375469 chr7 29186231 0.28 5.29E-15 cgl7235702 chr7 54956419 0.31 2.185E-25 cg20101352 chr7 29186234 0.30 7.126E-15 cg01691182 chr7 55639118 0.21 6.931E-21 cgl8451588 chr7 29606289 0.21 6.837E-20 cg02589791 chr7 63955666 0.28 3.604E-19 cgll855325 chr7 30029717 0.21 1.655E-14 cgl8753440 chr7 63955786 0.29 9.218E-21 cgl3366537 chr7 30029754 0.22 4.174E-14 cgl4871601 chr7 64030039 0.21 3.894E-14 cgl7988320 chr7 30361459 0.21 5.08E-18 cg00368636 chr7 64734674 0.25 1.435E-20 cgl2999366 chr7 30499283 0.21 1.187E-21 cgl0864952 chr7 65671987 0.22 8.907E-18 cg09333221 chr7 30804200 0.25 1.106E-19 cgl8550262 chr7 72812030 0.20 8.809E-19 cg08946731 chr7 32981826 0.28 2.098E-20 cgl2210255 chr7 72838671 0.23 7.463E-19 cg26905768 chr7 34098803 0.21 3.703E-20 cgl3598010 chr7 72838776 0.28 1.739E-19 cg08959216 chr7 35293309 0.22 6.818E-17 cg01292793 chr7 73002385 0.27 1.158E-23 cg26673012 chr7 35293753 0.21 2.509E-14 cgl4115936 chr7 73002496 0.20 6.52E-22 cgl7985646 chr7 35293759 0.29 1.489E-14 cgl3337731 chr7 73011308 0.26 3.125E-19 cg01688536 chr7 35296968 0.24 2.14E-18 cg21043424 chr7 73300908 0.22 3.181E-22 cg08732352 chr7 35298391 0.20 1.117E-16 cg26311610 chr7 73593138 0.20 2.573E-20 cg05809668 chr7 35301188 0.26 1.927E-17 cg25714115 chr7 73895061 0.21 3.052E-15 cgl5174623 chr7 35494345 0.22 6.924E-21 cg04376123 chr7 73895109 0.21 3.001E-17 cg26234658 chr7 36343787 0.22 4. IE- 20 cg22525688 chr7 74001908 0.24 3.728E-21 cg07239592 chr7 39453625 0.22 3.216E-15 cg20544372 chr7 74064549 0.20 1.044E-17 cg05858889 chr7 39649224 0.20 4.059E-20 cg03069204 chr7 75535491 0.35 1.48E-25 cg21101743 chr7 39649254 0.27 1.082E-21 cg04652097 chr7 79083445 0.25 6.597E-21 cg06890747 chr7 39649290 0.28 1.403E-20 cg08641579 chr7 79083447 0.23 4.009E-20 cgl2457909 chr7 39649359 0.25 1.356E-18 cg02523844 chr7 79083507 0.22 3.196E-17 cg27071152 chr7 39649443 0.32 5.617E-20 cg24021956 chr7 79083509 0.26 1.813E-19 cg25726664 chr7 42277807 0.31 1.698E-22 cg07448060 chr7 79083753 0.21 1.647E-17 cgl7588800 chr7 42278067 0.22 4.518E-20 cg06653026 chr7 84892267 0.23 8.384E-23 cg24497732 chr7 42278077 0.23 2.093E-21 cg04996195 chr7 87105398 0.20 1.704E-15 cg01399219 chr7 44145110 0.23 6.387E-22 cglll54552 chr7 87848242 0.27 2.809E-16 cgl0201685 chr7 44315903 0.25 1.399E-19 cgl9228034 chr7 92672812 0.26 6.688E-24 cg22132788 chr7 45002486 0.21 7.122E-15 cgl8209323 chr7 92672878 0.23 6.709E-20 cgl8500300 chr7 45128199 0.21 1.784E-23 cg26122451 chr7 92672950 0.23 1.082E-21 cg24676071 chr7 45613410 0.26 8.966E-20 cgl9414980 chr7 92673176 0.25 2.431E-23 cg26459372 chr7 45613676 0.26 1.579E-20 cg22579075 chr7 94250352 0.21 6.363E-18 cgl3523557 chr7 45613725 0.23 3.594E-16 cgl9678392 chr7 94953810 0.23 6.016E-16 cg26559707 chr7 47367816 0.21 4.021E-18 cgl7330251 chr7 94953956 0.23 8.036E-15

_

cg08167951 chr7 95025611 0.25 2.122E-18 cg20583316 chr7 100770476 0.25 1.1E-24 cg07121856 chr7 95025736 0.33 9.336E-19 cg25260543 chr7 100946792 0.23 1.239E-19 cg23230584 chr7 95025740 0.34 5.387E-20 cg05910443 chr7 101688675 0.27 1.616E-21 cg08520743 chr7 95025829 0.24 5.595E-17 cg03310939 chr7 101688730 0.27 6.01E-23 cg08828819 chr7 95025836 0.22 4.147E-16 cg02724472 chr7 102553293 0.25 2.693E-21 cg04685170 chr7 95025855 0.22 2.276E-18 cg27481555 chr7 102553369 0.23 1.345E-19 cgl5500865 chr7 95025924 0.25 1.261E-18 cg20442697 chr7 102553432 0.25 6.534E-22 cg25161512 chr7 95026066 0.23 6.623 E- 20 cg20485874 chr7 102553437 0.21 2.666E-19 cgll435506 chr7 95026073 0.32 3.42E-20 cgl9561297 chr7 102553457 0.29 1.886E-21 cg27413563 chr7 95026090 0.30 1.333E-19 cg00365499 chr7 104909430 0.21 4.065E-17 cg03301582 chr7 95026095 0.32 2.145E-19 cgll617147 chr7 105517689 0.27 2.731E-14 cg08898155 chr7 95026097 0.27 1.545E-17 cgl8664667 chr7 105517962 0.22 5.327E-16 cg04080282 chr7 95026106 0.25 1.638E-19 cg25813290 chr7 108767676 -0.22 4.984E-19 cg22421859 chr7 96622042 0.26 4.653E-14 cg25274503 chr7 116140128 0.34 1.185E-24 cg02990291 chr7 96625586 0.21 1.296E-14 cgl0062049 chr7 116140267 0.25 8.061E-24 cgl3209441 chr7 96626151 0.23 9.707E-19 cgl6260298 chr7 116140342 0.34 5.938E-24 cgll070059 chr7 96626399 0.21 7.428E-17 cgl2739419 chr7 116140593 0.27 2.264E-24 cg25825506 chr7 96626659 0.23 3.906E-18 cg07838272 chr7 116164670 0.25 1.07E-18 cg21545390 chr7 96627190 0.21 4.048E-14 cgl7469978 chr7 116164704 0.28 8.471E-20 cg25930591 chr7 96627602 0.21 9.735E-17 cg24980893 chr7 116164709 0.26 1.123E-17 cgl9722748 chr7 96627700 0.21 4.502E-18 cg07168526 chr7 116797907 0.21 3.358E-21 cg25797887 chr7 96627821 0.21 5.857E-15 cgl7204129 chr7 117119601 0.28 2.088E-19 cg06581175 chr7 96632635 0.23 1.253E-17 cgl7616554 chr7 117119611 0.28 5.947E-19 cgl7199800 chr7 96632777 0.22 5.748E-18 cg09626894 chr7 117119637 0.29 2.426E-19 cg01680010 chr7 96647117 0.26 4.714E-14 cg21461649 chr7 117119938 0.24 1.399E-18 cg08101303 chr7 96652222 0.27 1.907E-18 cg00735923 chr7 117119963 0.31 3.476E-20 cg24115040 chr7 96652375 0.25 1.012E-20 cg06081199 chr7 117120064 0.21 1.277E-19 cgl9451167 chr7 96655981 0.21 2.331E-17 cg27603796 chr7 117512803 0.21 9.899E-21 cg09910635 chr7 97361026 0.29 2.455E-23 cg08545129 chr7 117854304 0.20 4.767E-17 cg09236284 chr7 97361114 0.35 4.774E-24 cg09505788 chr7 117854511 0.23 1.8E-16 cg02539083 chr7 97361148 0.31 2.244E-24 cg03913921 chr7 120496827 0.26 6.456E-19 cg07550362 chr7 97361201 0.30 6.411E-21 cg06553841 chr7 120628572 0.22 3.299E-14 cg01287975 chr7 97361241 0.32 3.442E-20 cgl6868298 chr7 120969033 0.22 2.365E-19 cgll873482 chr7 97361244 0.35 1.385E-19 cg05470554 chr7 120969079 0.25 7.252E-20 cgl7437939 chr7 97361252 0.36 5.895E-22 cgl3161961 chr7 120970240 0.21 1.806E-14 cgl6288089 chr7 97361408 0.33 2.735E-20 cg27393010 chr7 121940216 0.25 2.04E-14 cg05165378 chr7 99155739 0.24 6.331E-15 cg02644510 chr7 121946608 0.21 1.5E-18 cg07484673 chr7 99155878 0.26 4.536E-17 cg20329153 chr7 121950282 0.20 1.438E-15 cgl2457529 chr7 99155892 0.23 1.175E-14 cg00158528 chr7 121956859 0.22 5.661E-15 cg22758700 chr7 99156126 0.28 4.218E-15 cgl8358894 chr7 121956890 0.23 1.09E-16 cg22531904 chr7 99595276 0.25 1.196E-16 cg26824006 chr7 121957254 0.24 8.935E-17 cg07693238 chr7 99595437 0.24 5.202E-17 cg25021359 chr7 123315035 0.23 9.744E-22 cg02327530 chr7 100091786 0.23 3.02E-19 cg27533119 chr7 124404472 0.23 4.567E-18 cgl6555537 chr7 100464771 0.24 5.01E-20 cg03764259 chr7 127176905 0.35 5.216E-23 cgl2507655 chr7 100465051 0.21 2.079E-18 cg00353923 chr7 127671044 0.23 1.406E-14 cg03568858 chr7 100465221 0.25 1.319E-24 cg07871590 chr7 127671193 0.27 4.372E-15 cg24075113 chr7 100465289 0.22 1.175E-20 cg27573591 chr7 127672152 0.20 1.665E-17 cg01274660 chr7 100465625 0.23 6.948E-21 cgl5087147 chr7 127672169 0.21 4.672E-20 cgl4020762 chr7 100465657 0.28 2.943E-21 cg04153784 chr7 127672235 0.23 3.542E-18 cg25149251 chr7 100488527 0.23 3.799E-17 cgl2628196 chr7 127672458 0.34 1.28E-19 cgl5575433 chr7 100488705 0.24 4.323E-19 cg09087503 chr7 127672473 0.36 5.246E-19 cg04156293 chr7 100488942 0.31 2.185E-20 cg09296001 chr7 127672564 0.42 2.983E-23 cg22488857 chr7 100489022 0.22 2.096E-18 cgl2345672 chr7 127672658 0.24 6.797E-16 cg20438404 chr7 100770192 0.21 4.796E-21 cg01337813 chr7 127808512 0.20 2.025E-19 cg02273392 chr7 100770414 0.23 7.717E-24 cgl2782180 chr7 127880932 0.22 1.261E-16

_

cg00840332 chr7 127881269 0.21 9.938E-15 cgll213690 chr7 149112402 0.35 2.161E-22 cgl9594666 chr7 127881280 0.21 2.044 E- 15 cg04487296 chr7 149389669 0.22 8.63E-16 cgl3381984 chr7 127881344 0.21 1.624E-17 cg21355828 chr7 149389814 0.26 3.14E-17 cg20372230 chr7 127911967 0.21 2.556E-16 cgl8177414 chr7 149389929 0.28 4.678E-16 cgl2829141 chr7 128000780 0.22 2.334E-16 cg26885268 chr7 149389941 0.26 1.426E-18 cg22491548 chr7 128000861 0.22 5.224E-16 cg07703462 chr7 149487338 0.27 8.252E-16 cgl3248778 chr7 128337725 0.32 3.266E-19 cg27455017 chr7 150037988 0.24 9.226E-19 cg26433034 chr7 128430626 0.23 3.383E-20 cgl7279839 chr7 150038598 0.27 2.593E-18 cgl8356974 chr7 128809100 0.21 9.871E-16 cg27494647 chr7 150038898 0.31 6.097E-20 cgl5835396 chr7 128809228 0.29 1.306E-15 cgl2914657 chr7 150413680 0.23 1.917E-21 cg03575641 chr7 128809442 0.24 1.695E-14 cgl4991769 chr7 150497157 0.22 6.881E-15 cg07687766 chr7 129421353 0.26 4.22E-17 cg08359956 chr7 150498205 0.21 9.183E-19 cg20186067 chr7 129422439 0.26 1.099E-17 cg05726600 chr7 150498594 0.21 2.138E-18 cgl9776616 chr7 129425330 0.24 7.478E-20 cg20142972 chr7 150652808 0.23 6.725E-21 cg01390574 chr7 129425451 0.31 1.23E-21 cgl4711997 chr7 150652864 0.31 2.431E-18 cg06314333 chr7 129425532 0.26 3.547E-17 cg20883831 chr7 150652948 0.39 4.679E-21 cgl5261247 chr7 129425731 0.25 2.536E-19 cgl8423852 chr7 150653001 0.30 3.268E-22 cgl0046388 chr7 129425858 0.23 1.282E-21 cgl5472092 chr7 150653079 0.36 8.155E-24 cgl3933043 chr7 130696871 0.20 2.354E-22 cgl8296036 chr7 150653115 0.29 5.201E-23 cg01919401 chr7 130985828 0.22 1.554E-18 cg24830730 chr7 150653195 0.35 2.894E-22 cgl6657340 chr7 131242787 0.25 1.339E-15 cg02961934 chr7 150896413 0.22 1.245E-19 cgl5127227 chr7 131242878 0.20 3.428E-14 cg06506863 chr7 150896449 0.21 3.47E-19 cgl4183329 chr7 131242962 0.21 8.758E-16 cg21532325 chr7 151107400 0.23 2.98E-19 cg06736785 chr7 132260175 0.24 4.184E-23 cgl6482474 chr7 151107637 0.30 1.782E-23 cgl3056495 chr7 134143249 0.28 8.051E-18 cgl9831077 chr7 151107924 0.23 2.753E-21 cg24059115 chr7 134143489 0.21 4.89E-15 cg07571734 chr7 151479894 0.23 4.026E-16 cgl6132520 chr7 134143906 0.24 3.845E-18 cg02432280 chr7 152622368 0.20 5.178E-18 cgl3801416 chr7 134143919 0.22 4.102E-15 cg06495961 chr7 153584582 0.22 3.024E-14 cg21079345 chr7 134144036 0.24 3.165E-19 cg03532926 chr7 153584839 0.25 1.133E-15 cg02215070 chr7 134144055 0.27 1.121E-19 cgl6476975 chr7 155164995 0.32 8.191E-16 cg08167706 chr7 134144106 0.34 1.937E-21 cgl2820681 chr7 155166290 0.23 1.172E-20 cg23918923 chr7 134144118 0.28 7.327E-19 cg27451484 chr7 155166435 0.21 1.047E-18 cg06390484 chr7 134575271 0.21 1.269E-21 cg20347882 chr7 155166554 0.22 9.54E-17 cgl9630629 chr7 136556193 0.21 3.784E-17 cg20567847 chr7 155167038 0.21 2.326E-15 cg06915773 chr7 137028165 0.23 9.833E-15 cg09134794 chr7 155252701 0.22 9.636E-15 cgll874123 chr7 137028198 0.21 2.334E-14 cg21497990 chr7 155255122 0.24 1.075E-18 cg06277657 chr7 137532374 0.21 8.792E-20 cg23426473 chr7 155255232 0.26 3.453E-20 cg08832906 chr7 139208852 0.27 2.463E-16 cgl6935980 chr7 155255310 0.23 1.139E-20 cg04935449 chr7 139208871 0.20 3.435E-14 cgl7278072 chr7 155258411 0.21 2.918E-16 cg24318763 chr7 139208979 0.23 8.844E-21 cg02892388 chr7 155260310 0.21 2.383E-17 cgl6107322 chr7 141211627 0.29 7.086E-26 cg09079818 chr7 155604091 0.26 2.138E-18 cg06331595 chr7 141211956 0.33 7.59E-26 cg07686872 chr7 156794879 0.22 8.069E-18 cg06334134 chr7 142986693 0.22 2.253E-16 cg01287054 chr7 156795156 0.22 8.525E-15 cg03514404 chr7 143579665 0.43 1.145E-22 cg07981013 chr7 156795767 0.20 1.724E-16 cg01030534 chr7 143579698 0.50 1.374E-23 cg26472133 chr7 156797104 0.23 1.753E-16 cg03225210 chr7 143579951 0.37 1.421E-25 cg25090972 chr7 156797988 0.23 1.212E-14 cg02245020 chr7 143580147 0.38 7.042 E-25 cg00143249 chr7 156798810 0.25 2.147E-18 cg09671837 chr7 143582308 0.27 1.597E-20 cg24717695 chr7 156809644 0.21 9.773E-18 cgl6807089 chr7 143582499 0.37 1.35E-22 cg09858188 chr7 156814480 0.30 4.515E-16 cg09846875 chr7 143582630 0.29 3.428E-25 cg00024086 chr7 156814491 0.20 2.843E-15 cg03789645 chr7 148394842 0.29 8.173E-22 cg02456451 chr7 156871073 0.26 1.316E-18 cglll09845 chr7 148394888 0.22 1.367E-17 cg00173659 chr7 156871088 0.26 2.779E-20 cg06899186 chr7 148394994 0.28 3.857E-16 cg22450968 chr7 156871234 0.28 5.889E-21 cg06592987 chr7 149112142 0.30 1.567E-22 cg07910560 chr7 157361396 0.23 2.497E-21 cgl6966315 chr7 149112318 0.30 1.717E-18 cg00099393 chr7 157361621 0.23 1.548E-21

_

cgll318054 chr7 157361692 0.32 6.707E-21 cgl4451926 chr8 23562918 0.22 3.977E-20 cg21606115 chr7 157361752 0.26 1.298E-21 cg01336781 chr8 23563182 0.22 1.534E-18 cg08022244 chr7 157361759 0.31 6.841E-22 cgl3021619 chr8 23563859 0.23 2.774E-15 cg01271455 chr7 157362062 0.30 1.033E-19 cgl4428146 chr8 23563925 0.25 2.443E-17 cg22395765 chr7 157362094 0.23 9.132E-20 cgl5854847 chr8 23563970 0.24 7.617E-19 cg06339573 chr7 157372262 0.20 4.023E-21 cg20892260 chr8 23564025 0.24 3.632E-20 cg02855778 chr7 157462914 0.22 5.541E-20 cgl3324546 chr8 23564031 0.22 7.699E-18 cgl0720723 chr7 157476443 0.24 7.897E-22 cg03694713 chr8 23564156 0.23 2.02E-17 cg26295921 chr7 157476575 0.20 1.656E-20 cg22747746 chr8 23564193 0.25 9.918E-19 cg04207084 chr7 157477846 0.31 6.413E-21 cgl0603004 chr8 23564294 0.20 1.466E-17 cg03515663 chr7 157478510 0.27 1.176E-23 cg03749016 chr8 23564591 0.21 5.916E-21 cg04937416 chr7 157479272 0.29 1.937E-25 cgl2165546 chr8 23566799 0.24 1.513E-20 cgl5572489 chr7 157481091 0.24 2.073E-21 cgl2812583 chr8 23567310 0.33 2.016E-18 cgl8004701 chr7 157481628 0.31 1.247E-21 cgll548303 chr8 23567350 0.23 7.226E-23 cgl6964025 chr7 157482215 0.30 1.03E-24 cg07143418 chr8 23567548 0.37 3.746E-20 cg22623223 chr7 157484045 0.23 8.589E-18 cg00258597 chr8 23567607 0.22 6.295E-22 cg07602744 chr7 157484164 0.30 1.656E-24 cgl3197216 chr8 23567658 0.22 1.934E-20 cgl8894200 chr7 157484250 0.21 2.177E-23 cg00126320 chr8 23584644 0.21 7.334E-19 cgl9241327 chr7 157484559 0.34 4.738E-22 cgl8026631 chr8 23584746 0.23 6.615E-16 cg27448110 chr7 157484647 0.26 2.272E-25 cgl4968300 chr8 23585186 0.20 1.833E-16 cg02006615 chr7 157485230 0.26 1.551E-23 cg23290344 chr8 24771466 0.30 1.273E-14 cg04059568 chr7 157486012 0.22 4.657E-18 cg24923694 chr8 25905747 0.22 2.489E-15 cgl8327157 chr7 157486718 0.23 8.563E-22 cgl8235000 chr8 26372829 0.24 1.648E-16 cg05124021 chr7 157487066 0.23 1.13E-19 cg26268277 chr8 26372879 0.20 3.652E-17 cgl4832998 chr7 157530956 0.31 2.118E-24 cgl7221758 chr8 30243241 0.23 3.178E-21 cg20670679 chr7 157561786 0.23 8.952E-17 cg00447833 chr8 30243260 0.27 1.977E-22 cg23168425 chr7 157561848 0.22 8.293E-18 cgl3455434 chr8 30243930 0.25 4.803E-20 cg23740652 chr7 157561925 0.21 8.095E-19 cg22431992 chr8 30244571 0.21 5.822E-15 cgl9013611 chr7 157668051 0.27 8.813E-22 cg24946597 chr8 31497464 0.22 1.187E-15 cgl5298059 chr7 157668141 0.23 2.005E-21 cgl2166610 chr8 31498256 0.24 1.121E-14 cgl2472483 chr7 157996945 0.22 1.71E-20 cgl9619014 chr8 37250930 0.20 2.517E-18 cg21914941 chr7 158261145 0.30 3.92E-24 cgl0705306 chr8 37337009 0.23 3.328E-19 cg05264279 chr7 158266136 0.20 2.573E-18 cgl3123964 chr8 38323238 0.35 1.139E-22 cgl4527439 chr7 158266198 0.22 1.884E-22 cg00400221 chr8 38323291 0.31 1.044E-22 cgl7764549 chr7 158287907 0.21 9.043E-21 cg21708058 chr8 38585602 0.26 4.785E-22 cgl9423622 chr7 158362729 0.31 1.761E-24 cg02388150 chr8 41165699 0.23 2.244E-17 cg22178238 chr7 158362809 0.26 3.615E-25 cgl9537719 chr8 41583498 0.23 1.258E-14 cg06631944 chr7 158365160 0.23 5.975E-23 cgll059357 chr8 41649676 0.20 7.141E-19 cg21038156 chr7 158936739 0.28 4.431E-15 cgl4904662 chr8 41655673 0.31 1.323E-23 cg08614290 chr7 158938491 0.22 9.588E-19 cg27498387 chr8 41655789 0.31 9.144E-23 cg23109344 chr8 496440 0.22 3.133E-18 cg25154801 chr8 41655826 0.25 7.633E-20 cg09159022 chr8 4849522 0.21 3.538E-16 cg00783104 chr8 41655894 0.21 1.358E-17 cg21762788 chr8 9756501 0.28 7.781E-19 cgl2091331 chr8 42065314 0.22 2.143E-17 cgl9403029 chr8 10587055 0.21 1.103E-17 cg02571142 chr8 42234803 0.21 3.521E-18 cg04844714 chr8 10872604 0.21 2.699E-19 cgl5936066 chr8 42356637 0.24 8.192E-21 cg06811478 chr8 10872626 0.21 2.98E-21 cg22855020 chr8 42356731 0.24 1.58E-22 cg26237168 chr8 10872648 0.24 5.832E-21 cgl0806146 chr8 42356871 0.20 4.958E-24 cgll377730 chr8 17270604 0.23 1.379E-17 cg03065447 chr8 49292486 0.39 3.207E-21 cgl4709253 chr8 17519419 0.22 6.531E-17 cgl4095438 chr8 49468684 0.28 1.557E-22 cgl2174804 chr8 18244861 0.26 2.701E-20 cg20527270 chr8 49468688 0.33 8.427E-23 cgl5232539 chr8 19459672 0.28 3.157E-18 cg04920358 chr8 49468800 0.28 6.507E-16 cgl7470251 chr8 19459996 0.20 4.304E-15 cgl8991611 chr8 49468828 0.37 1.774E-15 cg01710189 chr8 22454888 0.21 7.146E-15 cgl4907769 chr8 49468941 0.27 2.672E-18 cg09535960 chr8 23193704 0.26 1.095E-21 cg25647300 chr8 49670412 0.26 2.084E-22 cg09042448 chr8 23260443 0.27 4.521E-21 cg01451808 chr8 49676562 0.25 1.778E-19

_

cg00301660 chr8 49783269 0.22 3.702E-23 cgl2926938 chr8 93114150 0.25 7.93E-17 cg21737226 chr8 53326668 0.20 2.354E-18 cg08268017 chr8 94712118 0.21 1.971E-19 cg05965392 chr8 53478624 0.24 1.31E-15 cgl7495087 chr8 96085689 0.24 1.803E-18 cg26205771 chr8 53851156 0.25 1.414E-18 cg21333674 chr8 96705765 0.26 1.999E-18 cg03475285 chr8 54789207 0.31 5.906E-24 cg03224572 chr8 97172012 0.22 4.026E-17 cgl2070159 chr8 54789325 0.30 7.23E-22 cgl4088921 chr8 98944936 0.28 6.467E-18 cg03348397 chr8 54789648 0.26 3.078E-20 cg03561565 chr8 99438624 0.26 1.235E-17 cg02639634 chr8 54792161 0.29 2.478E-24 cgl4486338 chr8 99440279 0.29 1.165E-20 cgll993173 chr8 54857695 0.22 1.224E-21 cgl4968543 chr8 99986964 0.24 1.004E-20 cg08044097 chr8 55371013 0.25 7.86E-20 cg20219381 chr8 101118083 0.23 6.301E-18 cgl5377283 chr8 55371369 0.22 5.629E-19 cg24848035 chr8 101118525 0.26 4.959E-18 cg06616729 chr8 55379248 0.22 3.975E-14 cg00090261 chr8 101118548 0.22 5.041E-17 cgl5427886 chr8 55379663 0.28 2.281E-17 cgl3045134 chr8 103741780 0.24 1.006E-18 cgl7643864 chr8 56852148 0.28 2.525E-22 cg26764250 chr8 104090700 0.25 1.327E-22 cg03388786 chr8 56852253 0.24 1.231E-19 cg07222863 chr8 104153592 0.22 4.157E-18 cg06248767 chr8 56852290 0.31 3.22E-22 cgl8168101 chr8 104153627 0.21 1.262E-19 cgl5836635 chr8 57025662 0.24 1.313E-14 cgl4025053 chr8 104153637 0.22 2.619E-19 cg04127342 chr8 57358130 0.20 1.512E-16 cg21131024 chr8 104153643 0.21 9.36E-19 cgl2877723 chr8 57358312 0.27 5.143E-19 cgl6419441 chr8 105478683 0.23 1.097E-19 cgl3247663 chr8 59058254 0.33 6.291E-25 cgl6783744 chr8 105478855 0.26 1.372E-16 cgl2615766 chr8 59058273 0.28 1.904E-22 cg09435415 chr8 105479383 0.21 4.676E-15 cgl2219325 chr8 59058585 0.23 2.993E-17 cgl8031596 chr8 108510292 0.23 5.261E-19 cg23881926 chr8 59058656 0.21 1.888E-17 cg27616227 chr8 108510314 0.23 1.521E-19 cgl7498803 chr8 61822428 0.42 6.178E-21 cgl8147485 chr8 110986685 0.24 4.886E-14 cg22340072 chr8 61822740 0.24 7.627E-17 cg07064711 chr8 117950335 0.23 3.761E-19 cg26761826 chr8 67419572 0.28 4.253E-22 cg07868721 chr8 117950348 0.21 2.374E-16 cg00613284 chr8 67419936 0.24 6.444E-23 cg05783185 chr8 119121281 0.26 7.3E-20 cg01824969 chr8 67875261 0.22 9.528E-16 cg05313153 chr8 119122430 0.24 6.357E-23 cgl4657834 chr8 67875441 0.24 3.961E-16 cg21602557 chr8 119122878 0.33 4.95E-18 cg09428251 chr8 68658408 0.25 1.727E-22 cg02534163 chr8 120650994 0.33 4.688E-20 cgl5202006 chr8 68658566 0.23 5.899E-27 cg04452959 chr8 120651190 0.27 3.499E-18 cg00725401 chr8 70945169 0.22 9.375E-19 cg02709432 chr8 120651236 0.31 1.13E-18 cg20113824 chr8 70946946 0.25 6.989E-22 cg02156680 chr8 120651317 0.26 9.557E-20 cgl8096722 chr8 70947218 0.22 1.653E-15 cg06998282 chr8 120651398 0.35 1.113E-18 cg26187308 chr8 70947440 0.21 2.071E-19 cgl4409958 chr8 120651652 0.27 1.086E-18 cg07860213 chr8 70982039 0.30 1.492E-17 cg09313482 chr8 120685317 0.22 4.964E-20 cg01295203 chr8 70984199 0.21 1.044E-18 cg09404551 chr8 121136951 0.24 1.72E-19 cgll229513 chr8 70984559 0.24 1.615E-20 cg26626663 chr8 121137879 0.22 1.491E-14 cg24809973 chr8 72468820 0.24 5.081E-17 cgl2065840 chr8 121138133 0.20 1.306E-14 cgl5816712 chr8 72630628 -0.21 7.982E-22 cg23586322 chr8 121138232 0.27 5.192E-17 cgl3620034 chr8 72755052 0.21 1.282E-16 cg06802522 chr8 124173231 0.21 8.066E-15 cg21183256 chr8 73163868 0.27 3.8E-16 cg26140475 chr8 126525558 0.21 6.128E-19 cg24164564 chr8 76317040 0.26 5.321E-17 cgl0215401 chr8 131058332 0.25 3.164E-21 cg25662926 chr8 77595359 0.22 1.398E-16 cg21674704 chr8 131455249 0.23 3.366E-15 cgl3721134 chr8 86350390 0.21 1.8E-14 cg26219092 chr8 134388022 0.23 3.403E-21 cg05355225 chr8 86350568 0.32 4.089E-20 cgl0631716 chr8 135469436 0.23 5.491E-17 cgl8674980 chr8 86350581 0.32 7.637E-19 cg00873517 chr8 136511832 0.23 5.368E-18 cg07560510 chr8 86350592 0.26 2.754E-17 cg26327804 chr8 140714489 0.21 2.467E-18 cg09435929 chr8 86350913 0.22 1.122E-16 cg08856529 chr8 140714586 0.25 6.085E-21 cg21346043 chr8 86351067 0.24 1.12E-18 cg04849842 chr8 140714610 0.32 1.172E-19 cgl5541630 chr8 87081770 0.20 9.916E-20 cgl2175729 chr8 140715540 0.26 7.791E-15 cg01676962 chr8 91997001 0.27 5.83E-24 cgl2170191 chr8 142069560 0.23 1.428E-18 cg00914041 chr8 91997810 0.24 1.737E-18 cg20799268 chr8 142275649 0.21 3.221E-15 cgl7649385 chr8 91997985 0.26 3.848E-19 cgl4150907 chr8 142275722 0.20 2.837E-15 cgl6683746 chr8 93113829 0.22 1.369E-19 cgl8343437 chr8 142528415 0.23 8.691E-16 Meth.

probe ID Chr. Position P-value probe ID Chr. Position P-value

Diff. _ Diff.

cg04893741 chr8 142692382 0.21 1.378E-19 cgl3670316 chr9 78507533 0.33 2.435E-18 cgl5630458 chr8 142986649 0.21 2.751E-18 cgl4448830 chr9 79627216 0.22 2.892E-15 cg22892110 chr8 144798631 0.23 5.43E-16 cgl8277979 chr9 79630127 0.23 5.249E-16 cg24013620 chr8 144798688 0.25 3.67E-17 cgl0422777 chr9 79631227 0.23 1.383E-20 cgl7068623 chr8 144853065 0.21 7.019E-15 cgl3713830 chr9 79631737 0.24 2.762E-22 cg25833672 chr8 144853229 0.22 2.335E-16 cgl3455410 chr9 79631906 0.21 2.281E-19 cgl6001422 chr8 145022842 0.31 1.234E-25 cgl4579864 chr9 79632225 0.20 5.519E-20 cg03280622 chr8 145023013 0.26 1.296E-22 cgl3390867 chr9 86717438 0.28 1.664E-21 cgl5628518 chr8 145025059 0.30 6.622E-17 cgl4555996 chr9 86785905 0.21 1.526E-20 cgl9893585 chr8 145025064 0.23 2.322E-16 cgl2972233 chr9 91605893 0.24 2.402E-19 cgl9672546 chr8 145025123 0.23 5.04E-19 cg20083676 chr9 91605999 0.24 1.267E-19 cg21672292 chr8 145025128 0.28 2.605E-20 cg01515543 chr9 92254510 0.22 1.365E-21 cgl2864389 chr8 145025178 0.26 1.756E-19 cg22828581 chr9 93880502 0.23 2.962E-16 cgl4913216 chr8 145033104 0.20 5.864E-17 cgl0065823 chr9 96108467 0.27 1.127E-19 cgl6663419 chr8 145033566 0.27 4.233E-22 cgl3398482 chr9 96715256 0.21 9.039E-17 cg20803796 chr8 145103842 0.28 7.147E-15 cgl4169333 chr9 96721468 0.23 5.466E-20 cg01760475 chr8 145104359 0.26 1.725E-14 cg09155774 chr9 96723033 0.20 3.282E-18 cgl5006175 chr8 145698660 0.26 1.512E-14 cgl4276379 chr9 97663142 0.26 4.331E-24 cg26895804 chr8 145917243 0.21 6.283E-19 cgl3717434 chr9 97854044 0.21 4.135E-20 cgl3550694 chr9 73835 0.23 4.241E-16 cgl3945224 chr9 98111970 0.25 1.153E-19 cgl8016181 chr9 117608 0.21 3.249E-19 cg05347878 chr9 98784231 0.21 1.221E-14 cgl3413955 chr9 842914 0.21 1.36E-17 cgl4018731 chr9 98784336 0.26 1.126E-17 cg07173635 chr9 971480 0.21 3.677E-18 cgl9113375 chr9 98784351 0.28 4.46E-18 cgl4189141 chr9 1042605 0.27 9.514E-19 cg00767010 chr9 99482094 0.23 3.93E-18 cgl7869514 chr9 1042770 0.22 3.736E-18 cgl4015656 chr9 100070142 0.26 4.379E-16 cgl4110111 chr9 4297626 0.27 7.356E-15 cgl4382750 chr9 100264941 0.27 9.43E-21 cgl3588086 chr9 6644369 0.26 9.167E-17 cg00282510 chr9 100611516 0.21 1.022E-16 cgl3849454 chr9 14348844 0.25 4.747E-14 cgl4574728 chr9 110187656 0.27 7.179E-17 cgl4530275 chr9 16705212 0.21 2.621E-21 cgl4367995 chr9 110253800 0.25 5.953E-19 cgl4553740 chr9 18976715 0.25 9.121E-26 cgl3514049 chr9 110495709 0.21 5.936E-22 cgl4442421 chr9 19788257 0.21 1.599E-17 cgl5083233 chr9 112810402 0.33 2.68E-24 cg07837260 chr9 19788564 0.20 2.087E-17 cg21171115 chr9 112887903 0.22 8.784E-18 cgl2840719 chr9 21968233 0.29 1.843E-21 cg06148685 chr9 113800909 0.22 5.061E-15 cgl3932029 chr9 23824172 0.21 3.934E-18 cgl4563260 chr9 113801320 0.27 4.774E-19 cgl4173147 chr9 27528300 0.29 2.534E-24 cgl4102988 chr9 113801337 0.28 7.512E-19 cg21249376 chr9 27528432 0.27 1.233E-14 cgl4092045 chr9 116450241 0.28 7.322E-20 cg22262168 chr9 27528999 0.34 2.691E-17 cgl6510793 chr9 116450346 0.23 1.877E-22 cg21244846 chr9 27529339 0.31 2.759E-18 cgl4515614 chr9 116969440 0.21 8.428E-20 cgl7727989 chr9 27529519 0.26 2.599E-17 cgl3601435 chr9 120507431 0.33 2.28E-16 cg04469167 chr9 27529907 0.21 7.254E-15 cg27207079 chr9 123656751 0.21 8.073E-19 cgl3507084 chr9 34555042 0.25 3.59E-20 cgl3569051 chr9 124051703 0.27 5.92E-26 cgl3947167 chr9 34555109 0.23 3.43E-21 cgl4611152 chr9 124463026 0.21 8.2E-22 cgl5271616 chr9 35490515 0.28 7.753E-19 cg24015249 chr9 124498633 0.24 2.578E-20 cg07116010 chr9 35646325 0.22 1.147E-15 cgl3928417 chr9 124498782 0.27 3.861E-23 cg26607748 chr9 35690226 0.23 1.194E-18 cgl4594187 chr9 124498961 0.33 1.516E-20 cg00918944 chr9 35908117 0.21 4.686E-21 cg25542041 chr9 124982087 0.21 8.858E-19 cg25813936 chr9 36276879 0.20 2.169E-17 cgl3490403 chr9 124982413 0.24 9.176E-17 cgl4221766 chr9 36818572 0.21 3.525E-16 cgl7930194 chr9 124982834 0.23 1.073E-19 cgl3482308 chr9 37002685 0.35 1.115E-20 cgl3648318 chr9 124991408 0.28 1.768E-15 cgl4270346 chr9 38026076 0.21 4.305E-22 cgl3620051 chr9 126759535 0.22 6.297E-19 cgl7195771 chr9 71789541 0.24 1.948E-21 cgl4093715 chr9 126776180 0.22 6.498E-20 cg00842351 chr9 71789653 0.27 8.541E-19 cgl4166485 chr9 126779370 0.20 4.321E-20 cgll656547 chr9 72658747 0.20 5.891E-18 cgl4425564 chr9 126794772 0.22 1.129E-17 cgl6832407 chr9 73736539 0.21 7.178E-17 cgl4071579 chr9 126794830 0.26 6.321E-16 cg21362478 chr9 78507352 0.28 7.11E-17 cgl4568259 chr9 127421654 0.28 1.117E-16

_

cgl3946341 chr9 128799328 0.23 1.522E-20 cgl6414561 chrX 25033893 0.20 9.774E-17 cgl4204784 chr9 129387231 0.22 3.123E-15 cgl7036062 chrX 25034037 0.29 1.607E-16 cgl2777520 chr9 129387303 0.24 4.669E-17 cgl8102233 chrX 25034093 0.29 2.584E-18 cgl4398661 chr9 129433779 0.21 5.281E-16 cg08769559 chrX 25034121 0.23 3.288E-16 cgl4635269 chr9 129439339 0.25 5.729E-18 cgl6507965 chrX 25034151 0.29 3.932E-16 cgl4281592 chr9 129884313 0.28 8.187E-23 cgl4514403 chrX 25034220 0.23 1.491E-17 cg08076018 chr9 129885080 0.27 6.52E-17 cgl8000886 chrX 25034241 0.27 1.132E-16 cg09427311 chr9 129885730 0.21 5.849E-16 cg21729122 chrX 25034488 0.24 9.029E-16 cg00188748 chr9 130564509 0.20 2.259E-21 cgl0994247 chrX 25035867 0.22 2.288E-14 cgl3458609 chr9 130608923 0.23 7.551E-22 cg22846914 chrX 25041258 0.29 2.305E-14 cg07950002 chr9 131465811 0.21 1.424E-14 cg00040455 chrX 30326676 0.23 1.57E-18 cgl4016177 chr9 131965610 0.22 3.056E-18 cgl5888279 chrX 30327778 0.20 8.292E-17 cg00118808 chr9 132097931 0.23 1.506E-21 cg27424407 chrX 34674190 0.22 1.774E-15 cgl4262955 chr9 132114769 0.22 8.798E-23 cg21918559 chrX 36976052 0.33 1.744E-17 cgl3972124 chr9 132539744 0.21 5.329E-22 cgl6337138 chrX 36976075 0.32 2.026E-16 cgl3463203 chr9 132961972 0.21 3.098E-20 cgl7407511 chrX 38080364 0.22 9.309E-17 cgll045524 chr9 133320781 0.28 7.689E-16 cg09287459 chrX 39548787 0.29 5.25E-19 cgl3597397 chr9 133320948 0.20 1.591E-14 cg08384999 chrX 40004346 0.21 3.734E-19 cgl3670057 chr9 133721945 0.22 2.212E-20 cg23851088 chrX 40004432 0.26 1.549E-20 cgl4288235 chr9 135036556 0.24 9.657E-20 cgl3943560 chrX 40004481 0.24 1.359E-20 cg02502361 chr9 135117928 0.25 6.32E-20 cg09340741 chrX 46432858 0.20 2.062E-14 cgl3646785 chr9 135461935 0.24 4.268E-19 cg03139204 chrX 46937658 0.22 3.259E-15 cg05001389 chr9 135853034 0.21 1.063E-18 cg07654896 chrX 46937829 0.25 4.846E-14 cgl4121282 chr9 137268074 0.24 1.505E-22 cgl8103394 chrX 47433374 0.22 3.258E-20 cgl4482968 chr9 137599175 0.21 1.917E-17 cg00406460 chrX 47433415 0.20 4.924E-14 cgl3914893 chr9 137980958 0.23 3.491E-23 cg25153755 chrX 47433716 0.31 1.649E-21 cgl3656173 chr9 139002093 0.27 1.832E-19 cgl8009325 chrX 47441605 0.21 3.774E-14 cg03607179 chr9 139236708 0.22 7.748E-25 cg27151711 chrX 47441773 0.31 3.901E-15 cgl4348741 chr9 139880223 0.28 5.507E-21 cgl6523424 chrX 47441779 0.22 1.112E-14 cgl4409810 chr9 140172908 0.21 4.835E-18 cg09515442 chrX 48689942 0.21 3.622E-15 cg03949008 chrX 2846196 0.26 1.141E-20 cg22332233 chrX 48897515 0.24 3.04E-20 cgl7028443 chrX 3630086 0.24 8.811E-19 cg04329736 chrX 48899020 0.21 4.167E-20 cgl5255584 chrX 8698502 0.22 4.732E-16 cgl0277365 chrX 49022793 0.23 4.489E-16 cg03184366 chrX 9984977 0.22 1.573E-21 cg25258879 chrX 49022996 0.27 2.909E-18 cgl4318199 chrX 12974511 0.31 1.305E-19 cgl4029629 chrX 49023064 0.22 1.037E-17 cg23083672 chrX 13587603 0.29 1.936E-23 cgl7670641 chrX 49023115 0.24 1.501E-17 cg00650640 chrX 13587678 0.37 1.742E-23 cg05740959 chrX 49087234 0.31 9.218E-21 cg00932276 chrX 13587976 0.28 1.226E-18 cgl6726201 chrX 49087385 0.24 1.36E-25 cgl2817924 chrX 13588162 0.26 2.03E-16 cgll590714 chrX 49832148 0.22 2.056E-20 cg07810164 chrX 13588174 0.24 8.073E-20 cgl2642693 chrX 50556917 0.24 1.417E-15 cg26310256 chrX 13588301 0.31 5.431E-24 cg06673178 chrX 50557022 0.23 2.776E-14 cg03810476 chrX 17392798 0.31 1.018E-24 cg25424856 chrX 50557036 0.22 3.716E-15 cg00409000 chrX 17395816 0.38 1.199E-20 cgl8110168 chrX 50557055 0.33 7.59E-16 cg24605338 chrX 17395856 0.37 1.982E-25 cg05152874 chrX 50557122 0.24 5.202E-17 cg20216854 chrX 19817872 0.28 4.806E-22 cg05947181 chrX 50557283 0.32 3.122E-19 cg02077027 chrX 19817931 0.22 7.846E-21 cgl2841929 chrX 50557522 0.27 2.24E-19 cgll721100 chrX 20134346 0.29 5.913E-20 cg25236484 chrX 51139247 0.22 2.159E-14 cg06016684 chrX 20134557 0.36 2.368E-20 cg08725455 chrX 53077301 0.22 3.876E-18 cg24001644 chrX 20134719 0.25 9.292E-16 cg02896496 chrX 54385394 0.23 3.678E-16 cg08812897 chrX 20286243 0.32 1.026E-21 cg20134598 chrX 54947308 0.21 1.378E-22 cgl3350478 chrX 20286613 0.24 3.303E-22 cg06942445 chrX 54947373 0.24 3.512E-20 cgl5854666 chrX 25029360 0.31 3.157E-17 cg02590710 chrX 56258440 0.25 5.08E-20 cgl6890879 chrX 25029629 0.26 8.44E-15 cg21327343 chrX 56258579 0.29 1.227E-21 cg22820312 chrX 25030326 0.21 6.218E-15 cgl9505129 chrX 56258695 0.21 1.504E-24 cg25053900 chrX 25033890 0.26 7.573E-15 cg22829182 chrX 56258808 0.24 1.366E-24

_

cg05559795 chrX 56258812 0.26 1.115E-25 cgl3397632 chrX 106750861 0.25 1.196E-17 cg09195491 chrX 56258900 0.25 6.739E-20 cg24275475 chrX 107681397 0.34 1.07E-26 cg03610137 chrX 56259040 0.22 4.543 E-23 cg05064925 chrX 107681469 0.39 1.85E-25 cg03834574 chrX 56259094 0.38 2.493E-22 cgl2737160 chrX 107681482 0.26 2.285E-22 cg06457357 chrX 56259243 0.38 5.926E-23 cg00815013 chrX 107681737 0.31 8.211E-28 cg06655100 chrX 56259373 0.31 8.795E-23 cg07553115 chrX 107976167 0.22 1.508E-16 cg24268343 chrX 56260186 0.22 5.462E-20 cg01992935 chrX 108868271 0.25 4.715E-14 cg06650847 chrX 63004884 0.23 2.634E-15 cg06720669 chrX 108868282 0.24 7.601E-15 cg22771999 chrX 64888437 0.29 2.974E-22 cg01289637 chrX 114468879 0.22 1.257E-15 cg08195538 chrX 67914130 0.28 3.664E-15 cgl6584431 chrX 117250153 0.20 2.013E-18 cgl7074762 chrX 68052208 0.23 2.084E-23 cg27062326 chrX 117629163 0.26 4.852E-17 cg02268650 chrX 68348465 0.25 1.694E-18 cg06130360 chrX 117633362 0.21 1.286E-15 cg06539694 chrX 68348545 0.20 2.845E-19 cg00114913 chrX 118107540 0.22 4.196E-16 cgl0510586 chrX 68348597 0.29 2.992E-18 cg08814148 chrX 118407645 0.23 3.442E-19 cgl7017670 chrX 68525613 0.29 9.563E-20 cg26375010 chrX 118407852 0.31 2.163E-19 cg06967228 chrX 68525725 0.28 3.572E-22 cg07749485 chrX 119124509 0.23 2.008E-15 cg24187351 chrX 68525883 0.29 2.855E-19 cg26822438 chrX 119134368 0.23 3.889E-17 cgll024449 chrX 70150787 0.24 3.555E-16 cg03738247 chrX 119134526 0.23 7.366E-17 cgll859529 chrX 70150922 0.31 5.74E-19 cgl2814550 chrX 119134684 0.32 1.045E-21 cg02053896 chrX 70151117 0.28 1.086E-22 cgl7527404 chrX 119135074 0.22 1.161E-16 cg20622056 chrX 70151134 0.24 3.762E-22 cgl2290635 chrX 119148809 0.29 2.221E-22 cg01758418 chrX 70151160 0.25 3.491E-20 cg23647037 chrX 119150375 0.27 8.522E-20 cgl3857811 chrX 70151209 0.30 1.826E-22 cgl6515238 chrX 119444909 0.31 8.638E-16 cg20346189 chrX 71524766 0.22 2.935E-15 cg04069374 chrX 119445076 0.21 2.953E-16 cgll932249 chrX 71524953 0.22 2.238E-15 cgl6692973 chrX 119445209 0.24 1.139E-17 cgl5850390 chrX 72668487 0.24 3.48E-21 cgl3204538 chrX 119445300 0.34 7.846E-20 cgl6863294 chrX 72668847 0.29 6.521E-16 cg23483251 chrX 119445319 0.26 6.796E-19 cg09210933 chrX 73641881 0.21 2.69E-18 cg09793609 chrX 119445399 0.24 3.442E-21 cg06805513 chrX 73641955 0.27 5.837E-20 cg21480420 chrX 119445407 0.24 2.344E-21 cg25943872 chrX 73642385 0.30 2.449E-24 cgl2384989 chrX 122317614 0.27 1.859E-14 cgl5236541 chrX 73642618 0.33 1.422E-22 cg20950932 chrX 122317633 0.23 1.407E-14 cg22750044 chrX 73642662 0.27 5.24E-24 cg21747330 chrX 122319602 0.21 1.566E-17 cgl9214916 chrX 73642734 0.29 2.949E-22 cg24447042 chrX 128657893 0.26 2.679E-17 cg08605656 chrX 73642885 0.23 1.059E-18 cg26348018 chrX 129087487 0.25 4.576E-20 cgl3788061 chrX 78623020 0.21 9.555E-15 cg06428055 chrX 129243872 0.28 1.218E-20 cg05911774 chrX 99899345 0.24 1.61E-19 cg23356769 chrX 129245245 0.23 7.068E-16 cgl6510657 chrX 100333950 0.27 1.965E-23 cg05911704 chrX 129304869 0.25 2.156E-18 cgl5198729 chrX 100446496 0.35 1.253E-23 cg24340926 chrX 129305036 0.25 1.127E-15 cgl0874556 chrX 100446569 0.28 1.18E-22 cg09407917 chrX 130192151 0.23 2.045E-16 cgl3114305 chrX 100446736 0.31 7.592E-22 cgl6084857 chrX 130216575 0.22 9.327E-18 cgl4457691 chrX 100740937 0.20 1.61E-15 cg05680973 chrX 132090141 0.21 1.516E-16 cg09278708 chrX 101905837 0.26 3.651E-21 cg05347431 chrX 132547568 0.24 1.282E-16 cg04748497 chrX 101906989 0.22 7.669E-20 cg27505047 chrX 133684884 0.20 3.267E-16 cg25950739 chrX 101907254 0.27 4.868E-21 cg22410382 chrX 134124941 0.24 1.794E-19 cg09789426 chrX 102000698 0.25 1.571E-17 cgll923788 chrX 134124955 0.25 8.731E-18 cgl3640071 chrX 102585147 0.20 4.297E-16 cg20549224 chrX 134124960 0.24 2.137E-15 cglll94545 chrX 105066793 0.24 3.418E-14 cgll458217 chrX 134125022 0.27 6.645E-16 cgl4951132 chrX 105067038 0.20 7.904E-16 cg03423123 chrX 134125181 0.26 4.796E-18 cg02580986 chrX 105421602 0.28 3.951E-19 cgl6955726 chrX 134125259 0.35 9.081E-18 cg02285579 chrX 106516174 0.26 4.085E-15 cg02773050 chrX 134654287 0.27 4.077E-20 cgl0593416 chrX 106750120 0.31 9.907E-19 cg26055054 chrX 134654347 0.21 1.603E-14 cg01765758 chrX 106750146 0.28 1.822E-17 cg21932800 chrX 135056858 0.26 5.422E-23 cgl9023309 chrX 106750168 0.30 8.159E-19 cg06711837 chrX 137792814 0.25 5.412E-21 cgll450947 chrX 106750342 0.40 2.21E-18 cg06525551 chrX 137792939 0.31 1.155E-20 cg05829338 chrX 106750612 0.22 9.499E-19 cg05196026 chrX 137793096 0.37 8.29E-19 Meth. Meth. probe ID Chr. Position P-value probe ID Chr. Position P-value

Diff. Diff.

cg06959635 chrX 138724627 0.24 5.119E-21 cg25129414 chrX 152848639 0.22 2.805E-20 cg25172243 chrX 138724688 0.24 3.408E-20 cg06616051 chrX 153094332 0.28 8.946E-21 cg21557231 chrX 138725077 0.26 1.971E-23 cg09329826 chrX 153094594 0.38 9.44E-24 cg08476890 chrX 138774601 0.22 2.571E-23 cgl2763824 chrX 153094947 0.24 4.339E-19 cg21306973 chrX 139584886 0.22 2.041E-15 cgl0320061 chrX 153094967 0.24 8.432E-19 cgll638117 chrX 139587335 0.28 1.593E-15 cg23497752 chrX 153598077 0.27 3.053E-24 cgl7156570 chrX 139592377 0.22 2.149E-17 cgl3365334 chrX 153598742 0.28 5.386E-22 cg24691854 chrX 139593162 0.22 5.695E-15 cg26540943 chrX 154842296 0.20 7.58E-15 cg27080287 chrX 139593505 0.29 5.279E-16 cg06659128 chrX 154842535 0.20 2.935E-16 cg01560464 chrX 142721195 0.23 1.731E-19 cg00763725 chrX 154842689 0.39 1.845E-21 cg05135828 chrX 142721385 0.31 3.347E-16 cgl2403148 chrX 154842718 0.37 1.907E-26 cg23297872 chrX 142721819 0.27 4.83E-15 cg07311845 chrX 154842736 0.32 5.726E-24 cg23690264 chrX 142721909 0.22 1.827E-14 cg09975171 chrX 154842841 0.25 1.726E-21 cg26943822 chrX 142723713 0.21 4.3E-15 cgl3654344 chrY 2654978 0.21 5.938E-18 cg21537736 chrX 149534089 0.21 2.689E-16 cg04169747 chrY 2655740 0.24 4.485E-19 cg25614853 chrX 149534258 0.23 2.402E-18 cgll898347 chrY 2655866 0.21 1.106E-16 cg05259868 chrX 150344204 0.23 4.492E-17 cg09595415 chrY 2655942 0.21 7.969E-17 cgl7032587 chrX 150903247 0.20 2.225E-20 cg05618150 chrY 7140718 0.36 1.219E-23 cg25528646 chrX 151143302 0.21 2.834E-14

Cell communication is the central functional entity of PCa methylation profile

Gene-set enrichment analysis of the CpG sites with differential methylation identified 466 enriched GO terms (biological processes) with a multiple testing corrected p-value<0.01 , considering the number of probes in every gene (Table 2). The most frequent terms in this list include various forms of cell-cell communications, growth, senescence, bone morphogenetic protein signaling, neurogenesis, and differentiation (Figure 4 and Figure 5). Protein interaction analysis of the differentially methylated promoters using the EpiMod algorithm identified a total of 9 genes as a hotspot for protein-protein interactions containing a minimum of 10 interacting partners and an FDR <0.01 (Table 3 and Table 4, Figure 6). Among these are genes known to be involved in

carcinogenesis, including C-X-C Motif Chemokine Ligand 5 ( CXCL5 ), Estrogen Related Receptor Gamma ( ESRRG ), and Sclerostin Domain Containing 1 ( SOSTDC1 ). The most active hotspot, however, was found for collagen type-3 alpha-1 ( COL3A1 ), located at the center of an interactive network of COL5A2, COL5A1, COL11A 1, COL11A2, PCOLCE, and HTRA1, all being members of extracellular matrix regulation pathways (Table 4, Figure 6).

Table 2. Gene ontology terms enriched in genes with differentially methylated CpGs. The“GO” column shows differentially methylated genes in GO and the PCa column shows differentially methylated genes in PCa.

Table 3.

interactions in prostate cancer.

C0L3A1 DDR1 HTRA1 PCOLCE DDR2 COL1 1 A2 COL11A1

1281 COL3A1 10 5.36

U COL5A2 COL5A1 LRP10

TRIP6 AQP1 HOXA1 HOXA9 KIAA1683 PTK2 PRKAA2 SYNGAP1

7205 TRIP6 20 4.17 0.005 LPAR2 PTPN13 CATSPER1 NUP210 ODF1 EFEMP2 ULK1 ODF2

SPAG4 CHIC2 PLEKHA1 ARHGAP29

n_n, MYF5 ID3 ID2 ID1 MYOG MDFIC MYF6 ELK4 MSC IFI16

4617 MYF5 11 3.17

^{0 01} TMEM173

n_n. CXCL5 CXCR1 CXCR2 CXCL6 CXCL3 CXCL2 ADRA1A GRIA1

6374 CXCL5 10 3.96

MY05B ADRA1 D

ITGA4 CD82 CD81 EED PRKACB MDK THBS2 EMILIN1 LGALS8

3676 ITGA4 23 4.00 0.002 CD53 JAM 2 ADAM28 ADAM 2 JAML MAD CAM 1 EMILIN2 PTGFRN

MS4A1 CLGN IFITM1 CR2 EZH1 AEBP2

Table 4. Network details of the Epi-Mods.

Methylation Methylation

EntrezID Gene difference P- EntrezID Gene difference P- value value

TXNRD1 (13 genes) 84171 LOXL4 0.001

1299 COL9A3 0.063

7296 TXNRD1 1.00E-18 8515 ITGA10 6.00E-04 10628 TXNIP 0.298 1290 COL5A2 2.00E-1 1 84988 PPP1 R16A 1.00E-05 1289 COL5A1 0.019 51022 GLRX2 0.071 26020 LRP10 0.15 56963 RGMA 4.00E-08 1690 COCH 0.015 3620 ID01 3.00E-07 1298 COL9A2 0.386 4062 LY6H 2.00E-04 5549 PRELP 0.863 79187 FSD1 0.021 4146 MATN1 0.232 55661 DDX27 0.461 4148 MATN3 0.096 64403 CDH24 0.208 2896 GRN 0.742 8796 SCEL 0.105 ESRRG (10 genes)

3133 HLA-E 0.812

29085 PHPT1 0.885 2104 ESRRG 3.00E-14 SPARC (28 genes) 133522 PPARGC1 B 0.34

22899 ARHGEF15 4.00E-09

6678 SPARC 2.00E-15 5629 PROX1 0.6 5154 PDGFA 0.487 2101 ESRRA 0.692 3339 HSPG2 0.135 8431 NR0B2 0.013 1305 COL13A1 0.003 1854 DUT 0.764 1281 COL3A1 3.00E-13 10957 PNRC1 0.364 1513 CTSK 3.00E-07 2494 NR5A2 0.097 51 18 PCOLCE 1.00E-07 3174 HNF4G 0.85 22795 NID2 2.00E-07 SOSTDC1 (33 genes)

4921 DDR2 1.00E-09

64856 VWA1 0.018 25928 SOSTDC1 9.00E-14 1302 COL11A2 1.00E-05 652 BMP4 1.00E-08 780 DDR1 0.063 650 BMP2 0.472 1301 COL11A1 0.011 659 BMPR2 0.622 1280 COL2A1 0.062 654 BMP6 0.032 5654 HTRA1 0.112 25805 BAMBI 2.00E-06 1311 COMP 2.00E-05 655 BMP7 0.001 Methylation Methylation

EntrezID Gene difference P- EntrezID Gene difference P- value value

9350 CER1 3.00E-05 3205 HOXA9 0.579 168667 BMPER 0.125 80726 KIAA1683 1.00E-09 9241 NOG 0.96 5747 PTK2 0.374 8646 CHRD 0.005 5563 PRKAA2 0.372 10468 FST 0.02 8831 SYNGAP1 0.001 1 1167 FSTL1 2.00E-09 9170 LPAR2 0.03 657 BMPR1A 2.00E-04 5783 PTPN13 0.542 64388 GREM2 0.161 117144 CATSPER1 0.173 26585 GREM1 0.435 23225 NUP210 0.055 83729 INHBE 1.00E-07 4956 ODF1 0.713 656 BMP8B 0.129 30008 EFEMP2 4.00E-06 220388 CCDC89 1.00E-08 8408 ULK1 0.139 4256 MGP 7.00E-07 4957 ODF2 0.082 729330 OC90 4.00E-06 6676 SPAG4 0.539 392255 GDF6 0.322 26511 CHIC2 0.666 1 1063 SOX30 0.52 59338 PLEKHA1 0.3 57045 TWSG1 0.21 9411 ARHGAP29 0.64 8200 GDF5 0.072 MYF5 (11 genes)

7092 TLL1 0.942

5654 HTRA1 0.112 4617 MYF5 2.00E-12 26020 LRP10 0.15 3399 ID3 0.002 2658 GDF2 2.00E-04 3398 ID2 0.763 4342 MOS 1.00E-06 3397 ID1 0.904 4046 LSP1 0.017 4656 MYOG 0.093 4009 LMX1A 8.00E-04 29969 MDFIC 1.00E-09 1066 CES1 0.633 4618 MYF6 3.00E-05 COL3A1 (10 genes) 2005 ELK4 0.004

9242 MSC 2.00E-06

1281 COL3A1 3.00E-13 3428 IFI16 0.991 780 DDR1 0.063 340061 TMEM173 5.00E-1 1 5654 HTRA1 0.112 CXCL5 (10 genes)

51 18 PCOLCE 1.00E-07

4921 DDR2 1.00E-09 6374 CXCL5 1.00E-1 1 1302 COL11A2 1.00E-05 3577 CXCR1 0.024 1301 COL11A1 0.011 3579 CXCR2 6.00E-04 1290 COL5A2 2.00E-11 6372 CXCL6 1.00E-13 1289 COL5A1 0.019 2921 CXCL3 0.002 26020 LRP10 0.15 2920 CXCL2 0.069

TRIP6 (20 genes) 148 ADRA1A 3.00E-05

2890 GRIA1 0.018

7205 TRIP6 1.00E-12 4645 MY05B 0.622 358 AQP1 1.00E-07 146 ADRA1 D 0.209 3198 HOXA1 0.241 ITGA4 (23 genes) Methylation Methylation

EntrezID Gene difference P- EntrezID Gene difference P- value value

10863 ADAM28 1.00E-05

3676 ITGA4 1.00E-10 2515 ADAM 2 0.015

3732 CD82 0.043 120425 JAML 4.00E-05

975 CD81 0.183 8174 MADCAM1 4.00E-06

8726 EED 0.589 84034 EMILIN2 0.009

5567 PRKACB 0.492 5738 PTGFRN 0.055

4192 MDK 0.169 931 MS4A1 0.21

7058 THBS2 0.25 1047 CLGN 0.492

1 11 17 EMILIN1 7.00E-10 8519 IFITM1 8.00E-09

3964 LGALS8 0.016 1380 CR2 0.281

963 CD53 9.00E-06 2145 EZH1 0.055

58494 JAM 2 0.015 121536 AEBP2 0.046

Genomic regions differentially methylated (DMRs) in PCa

Using a bump hunting approach, we found 613 genomic coordinates containing a minimum of 3 consecutive CpGs, an average regional methylation difference >0.2, and a family-wise error rate (FWER) <0.01 (Table 5). All of these regions were hypermethylated, and the vast majority was mapped to coding genes and CpG Islands. Among the largest and most differentially methylated segments are hypermethylation in the promoters of tumor suppressors ( APC , 10 probes, 30%; KLK10, 4 probes, 28%), genes involved in regulation of cellular senescence ( HIF3A , 8 probes, 31%), cell communication and adhesion (Protocadherin gene cluster [n=88], 3-9 probes, 21-36%), and genes regulating the growth including PDE4D (6 probes, 23%) and estrogen receptor-related gamma ( ESRRG , 6 probes, 24%). In addition, a number of chromatin regulators such as histone deacetylase 9 ( HDAC9 , 6 probes, 26%) and TET1 (4 probes, 31%), as well as genes coding for histone subunits ( HIST1H-1A , 3G, 4D & 4F) were found to show increased methylation in their promoters (3-7 probes, 22-27%).

Table 5. DMRs in prostate cancer.

chr1 3514921 3515194 274 0.26 3 0 0 2802 MEGF6

chr1 6663664 6664268 605 0.24 4 0.001 9487 0

chr1 8277394 8277746 353 0.25 3 0.001 106643 0

chr1 9129487 9129648 162 0.25 3 0.001 0 1954 SLC2A5

chr1 9884600 9884732 133 0.25 5 0 49 0

chr1 24648696 24649398 703 0.25 4 0 0 0 GRHL3

chr1 151 103642 151104003 362 0.25 3 0.001 12634 0 chr1 155290535 155290813 279 0.22 5 0.003 0 0 RUSC1 chr1 155290535 155290813 279 0.22 5 0.003 0 0 RUSC1-AS1 chr1 156358231 156358408 178 0.28 3 0 3217 0

chr1 169396637 169396909 273 0.34 8 0 0 0 CCDC181 chr1 197882170 197882469 300 0.24 3 0.002 0 532 LHX9 chr1 200003342 200005453 2112 0.25 12 0 0 0 NR5A2 chr1 204329081 204329158 78 0.24 3 0.001 23 17574

chr1 208132388 208132787 400 0.28 4 0 62800 0

chr1 2130901 16 213090240 125 0.23 3 0.003 58635 33407

chr1 217311014 217311547 534 0.24 6 0.001 0 0 ESRRG chr1 246952215 246952508 294 0.30 4 0 0 0 LINC01341 chr10 3108651 3109053 403 0.29 3 0 751382 0

chr10 8097183 8097354 172 0.26 3 0 0 0 GAT A3 chr10 11206772 11206870 99 0.25 6 0 0 308 CELF2 chr10 18549536 18549778 243 0.25 3 0.001 0 1 19301 CACNB2 chr10 26223100 26223310 211 0.21 3 0.007 0 0 MY03A chr10 28035631 28036151 521 0.23 8 0 852 419

chr10 30724020 30724274 255 0.25 4 0 0 312 MAP3K8 chr10 43697849 43698141 293 0.38 4 0 0 0 RASGEF1A chr10 45914276 45914949 674 0.32 7 0 0 0 ALOX5 chr10 52177823 52178225 403 0.26 4 0 0 0 SGMS1 chr10 70321383 70321580 198 0.31 4 0 0 560 TET1 chr10 73846858 73847259 402 0.23 3 0.003 0 0 ANAPC16 chr10 73846858 73847259 402 0.23 3 0.003 0 0 SPOCK2 chr10 73848153 73848458 306 0.22 3 0.006 0 0 ANAPC16 chr10 73848153 73848458 306 0.22 3 0.006 0 0 SPOCK2 chr10 81003020 81003657 638 0.21 3 0.008 0 0 ZMIZ1 chr10 88730946 88731295 350 0.23 3 0.003 0 0 AGAP11 chr10 93646991 93647648 658 0.25 6 0 21758 0

chr10 94825547 94825667 121 0.26 3 0 0 0 CYP26C1 chr10 94826053 94826319 267 0.24 3 0.001 0 0 CYP26C1 chr10 95517498 95517562 65 0.25 3 0.001 54584 54997

chr10 99473085 99473224 140 0.26 3 0 26069 0

chr10 100993553 100993587 35 0.23 4 0.004 0 233 HPSE2 chr10 101279697 101280523 827 0.31 5 0 12166 0

chr10 102419564 102419617 54 0.23 3 0.002 129927 0

chr10 102589840 102590225 386 0.22 3 0.005 147353 0

chr10 102893925 102894148 224 0.29 4 0 0 0 TLX1 chr10 102899949 102900130 182 0.26 3 0 2402 0

chr10 102905681 102906057 377 0.33 3 0 8134 0

chr10 102996254 102996464 211 0.22 3 0.004 0 0 LBX1-AS1 chr10 103043991 103044194 204 0.25 3 0 45374 0

chr10 103880979 103881480 502 0.24 5 0 11306 350

chr10 119000215 119000638 424 0.22 3 0.004 0 0 SLC18A2 chr10 123356236 123356336 101 0.21 3 0.007 0 280 FGFR2 chr10 123922863 123923450 588 0.31 8 0 0 0 TACC2 chr1 1 2904951 2905372 422 0.27 3 0 0 0 CDKN1C chr1 1 3181446 3181928 483 0.32 5 0 0 0 OSBPL5 chr1 1 19736150 19736333 184 0.24 5 0.001 0 829 LOC100126784 chr1 1 19736150 19736333 184 0.24 5 0.001 0 829 NAV2 chr1 1 20618198 20618250 53 0.31 3 0 436327 0

chr1 1 27015656 27015991 336 0.26 5 0 0 368368 FIBIN chr1 1 35160330 35160462 133 0.25 3 0 0 0 CD44 chr1 1 35639492 35639632 141 0.25 3 0 102 0

chr1 1 46317036 46317577 542 0.25 4 0.001 0 0 CREB3L1 chr1 1 46383066 46383209 144 0.23 3 0.004 0 4696 DGKZ chr1 1 47278977 47279586 610 0.24 5 0 0 8343 NR1 H3 chr1 1 57194120 57194562 443 0.28 4 0 0 0 SLC43A3 chr1 1 58940866 58941415 550 0.30 4 0 0 0 DTX4 chr1 1 61283968 61284417 450 0.26 3 0 0 0 SYT7 chr1 1 62691066 62691452 387 0.26 4 0 2053 0

chr1 1 63258712 63258744 33 0.24 4 0.002 31 0

chr1 1 63828672 63828762 91 0.25 3 0 0 24041 MACROD1 chr1 1 66326767 66327000 234 0.22 3 0.005 0 0 ACTN3 chr1 1 67350976 67351786 811 0.29 6 0 0 0 GSTP1 chr1 1 70508180 70508410 231 0.23 3 0.003 0 0 SHANK2 chr1 1 76033097 76033391 295 0.28 3 0 122677 0

chr1 1 89867653 89867819 167 0.24 5 0.001 0 80696 NAALAD2 chr1 1 105480979 105481292 314 0.22 3 0.005 0 0 GRIA4 chr1 1 111169457 111169865 409 0.24 4 0.001 0 0 COLCA2 chr1 1 1 11 169457 11 1169865 409 0.24 4 0.001 0 0 COLCA1 chr1 1 111383515 111383603 89 0.23 3 0.003 59 0

chr1 1 1 11410960 11 1411076 117 0.23 3 0.002 156 0

chr1 1 11141 1216 111411381 166 0.28 3 0 0 0 LAYN chr1 1 1 11847475 11 1847747 273 0.23 3 0.003 0 180 DIXDC1 chr1 1 116371188 116371781 594 0.26 5 0 247104 0

chr1 1 1 17069780 117069859 80 0.23 3 0.002 0 19545 LOC100652768 chr12 2944163 2944493 331 0.26 6 0 0 22035 NRIP2 chr12 8088818 8088937 120 0.22 3 0.004 0 34409 SLC2A3 chr12 14720805 14720858 54 0.23 3 0.004 69107 0

chr12 22487219 22487459 241 0.27 3 0 0 0 ST8SIA1 chr12 47219705 47219797 93 0.25 4 0.001 0 5115 SLC38A4 chr12 48591673 48592270 598 0.32 3 0 11963 0

chr12 50297477 50297793 317 0.29 5 0 0 0 FAIM2 chr12 52258077 52258264 188 0.23 3 0.002 23528 0

chr12 52400907 52401523 617 0.31 4 0 0 0 GRASP chr12 52626814 52627047 234 0.23 6 0.001 0 0 KRT7 chr12 53183930 53184086 157 0.31 4 0 0 0 KRT3 chr12 53359155 53359506 352 0.24 3 0.001 12469 0

chr12 53612551 53613154 604 0.27 4 0 0 562 RARG chr12 54071090 54071194 105 0.26 5 0 33707 0

chr12 54409485 54409657 173 0.26 5 0 2939 771

chr12 54424085 54424964 880 0.23 5 0.001 0 0 HOXC4 chr12 54424085 54424964 880 0.23 5 0.001 0 0 HOXC5 chr12 54424085 54424964 880 0.23 5 0.001 0 0 HOXC6 chr12 54447136 54447283 148 0.27 4 0 0 461 HOXC4 chr12 54447349 54448090 742 0.26 7 0 0 0 HOXC4 chr12 54653364 54653427 64 0.29 3 0 0 19895 CBX5 chr12 63025490 63026424 935 0.26 7 0 11338 0

chr12 65219392 65220152 761 0.27 4 0 0 248 TBC1D30 chr12 81471419 81472118 700 0.25 11 0 0 0 ACSS3 chr12 89744471 89744609 139 0.22 4 0.005 0 559 DUSP6 chr12 89744662 89744877 216 0.29 3 0 0 291 DUSP6 chr12 95941869 95941988 120 0.32 3 0 0 0 USP44 chr12 100750652 100750702 51 0.25 3 0 16737 89005

chr12 10331 1088 103311596 509 0.26 7 0 0 0 PAH chr12 104609432 104609797 366 0.32 6 0 0 0 TXNRD1 chr12 104852151 104852446 296 0.35 4 0 0 0 CHST11 chr12 106533667 106533898 232 0.26 5 0 0 0 NUAK1 chr12 108168987 108169333 347 0.23 3 0.002 0 0 ASCL4 chr12 1 11 127139 11 1127533 395 0.24 3 0.001 0 0 HVCN1 chr12 115136072 115136308 237 0.31 12 0 285434 0

chr12 1 16036878 116037223 346 0.25 3 0.001 934003 146882

chr12 120242394 120242513 120 0.22 3 0.005 0 160 CIT chr12 124246434 124247223 790 0.25 7 0 0 0 DNAH10 chr12 125140105 125140249 145 0.26 3 0 121924 5196

chr13 20735532 20735860 329 0.25 3 0.001 348 0

chr13 28541 142 28541477 336 0.25 3 0 0 0 CDX2 chr13 36045201 36045281 81 0.22 3 0.005 0 0 NBEA chr13 36919409 36919960 552 0.28 6 0 0 0 SPART chr13 43566114 43566618 505 0.27 10 0 0 0 EPSTI1 chr13 74707145 74707400 256 0.29 3 0 0 601 KLF12 chr13 95620874 95620997 124 0.29 3 0 256484 0

chr13 96204870 96205295 426 0.27 6 0 0 0 CLDN10 chr13 97646341 97646736 396 0.26 4 0 0 0 OXGR1 chr13 97646803 97647084 282 0.23 3 0.002 147005 65

chr13 100547249 100547331 83 0.25 3 0.001 0 0 CLYBL chr13 100641409 100641867 459 0.25 4 0.001 2389 0

chr14 21539712 21540329 618 0.24 3 0.002 0 0 ARHGEF40 chr14 22004993 22005368 376 0.28 4 0 0 25293 SALL2 chr14 23834808 23836012 1205 0.26 11 0 0 0 EFS chr14 24641070 24641201 132 0.25 7 0 8223 0

chr14 24803679 24804342 664 0.30 10 0 0 0 ADCY4 chr14 24837836 24838126 291 0.24 4 0.001 0 0 NFATC4 chr14 29235092 29235196 105 0.24 4 0.001 1081 0 chr14 29254853 29254961 109 0.23 3 0.003 0 0 LINC01551 chr14 36983518 36983737 220 0.23 4 0.004 0 0 SFTA3 chr14 38679643 38680313 671 0.24 4 0.001 0 0 SSTR1 chr14 38724648 38724945 298 0.27 3 0 0 0 CLEC14A chr14 52536147 52536436 290 0.23 3 0.004 200 0

chr14 57261886 57262177 292 0.26 3 0 16546 0

chr14 57278710 57279115 406 0.26 3 0 0 0 OTX2-AS1 chr14 60973823 60974039 217 0.24 3 0.001 21058 0

chr14 70653719 70654290 572 0.29 5 0 0 805 SLC8A3 chr14 91580429 91580613 185 0.23 5 0.001 0 52876 DGLUCY chr14 95234826 95235489 664 0.24 7 0 0 0 GSC chr14 95239570 95240143 574 0.25 4 0 3070 0

chr15 33009409 33009531 123 0.24 3 0.002 20110 0

chr15 37389951 37390284 334 0.28 3 0 0 0 MEIS2 chr15 41805273 41805946 674 0.28 4 0 0 0 LTK chr15 45421998 45422325 328 0.25 7 0 0 0 DUOX1 chr15 45421998 45422325 328 0.25 7 0 0 0 DUOXA1 chr15 45670865 45670875 11 0.28 3 0 0 0 GATM chr15 48938347 48938576 230 0.23 3 0.002 361 0

chr15 51385916 51386254 339 0.25 3 0 0 0 TNFAIP8L3 chr15 60690667 60690974 308 0.30 4 0 20833 0

chr15 68121028 68121563 536 0.24 3 0.001 0 0 SKOR1 chr15 74218697 74218733 37 0.21 3 0.007 0 0 LOXL1 -AS1 chr15 74658244 74658573 330 0.31 5 0 0 0 CYP11A1 chr15 8331691 1 83317306 396 0.20 3 0.008 0 0 CPEB1-AS1 chr15 83953744 83953775 32 0.23 3 0.004 147632 0

chr15 89438208 89438964 757 0.28 8 0 0 0 HAPLN3 chr15 89952052 89952904 853 0.26 7 0 61733 0

chr15 90039582 90039913 332 0.31 9 0 0 0 RHCG chr16 1030561 1030586 26 0.23 3 0.003 0 0 LMF1 chr16 3062382 3062795 414 0.24 5 0.001 0 884 CLDN9 chr16 3079708 3079953 246 0.22 4 0.004 0 0 BICDL2 chr16 3237964 3238423 460 0.26 3 0 15823 382

chr16 19894948 19895321 374 0.31 3 0 0 0 GPRC5B chr16 23847325 23847568 244 0.26 3 0 0 0 PRKCB chr16 25704296 25704507 212 0.32 3 0 0 0 HS3ST4 chr16 29888571 29888733 163 0.21 3 0.007 0 254 SLX1 B-SULT1A4 chr16 29888571 29888733 163 0.21 3 0.007 0 254 SEZ6L2 chr16 29888571 29888733 163 0.21 3 0.007 0 254 SMG1 P2 chr16 29888571 29888733 163 0.21 3 0.007 0 254 SLX1A chr16 29888571 29888733 163 0.21 3 0.007 0 254 BOLA2 chr16 29888571 29888733 163 0.21 3 0.007 0 254 LOC606724 chr16 29888571 29888733 163 0.21 3 0.007 0 254 LOC613038 chr16 31214417 31214607 191 0.27 4 0 0 129 PYCARD-AS1 chr16 51185110 51 185147 38 0.22 3 0.006 0 0 SALL1 chr16 54968727 54969146 420 0.24 5 0.001 5625 921

chr16 54970302 54971007 706 0.21 3 0.007 7200 0

chr16 56672387 56672525 139 0.25 3 0.001 0 0 MT1A chr16 66612955 66613096 142 0.25 3 0 0 0 CKLF-CMTM1 chr16 66612955 66613096 142 0.25 3 0 0 0 CMTM1 chr16 67203753 67204807 1055 0.28 7 0 0 0 HSF4 chr16 67203753 67204807 1055 0.28 7 0 0 0 NOL3 chr16 79623618 79623751 134 0.25 4 0 377053 0

chr16 88717134 88717755 622 0.29 12 0 0 0 CYBA chr17 873255 873452 198 0.22 3 0.005 0 8281 NXN chr17 5019638 5019761 124 0.22 3 0.005 0 0 ZNF232 chr17 5019638 5019761 124 0.22 3 0.005 0 0 USP6 chr17 6899207 6899310 104 0.23 3 0.002 0 0 ALOX12-AS1 chr17 12877227 12877772 546 0.25 4 0.001 0 0 ARHGAP44 chr17 19290503 19290690 188 0.22 3 0.004 0 7961 MFAP4 chr17 27917879 27918338 460 0.28 5 0 0 0 ANKRD13B chr17 29249485 29250073 589 0.22 3 0.005 0 0 ADAP2 chr17 33701321 33701353 33 0.24 3 0.001 36727 0

chr17 35014412 35014588 177 0.22 3 0.005 49004 0

chr17 38465281 38465510 230 0.26 7 0 0 7448 RARA chr17 41363597 41364007 411 0.34 9 0 0 0 TMEM106A chr17 41363597 41364007 411 0.34 9 0 0 0 NBR1 chr17 42386190 42386419 230 0.25 4 0.001 0 0 RUNDC3A chr17 43221220 43221575 356 0.31 4 0 0 352 ACBD4 chr17 43449055 43449285 231 0.23 3 0.004 1390586 0

chr17 43974344 43975063 720 0.29 7 0 864808 0

chr17 44896080 44896166 87 0.22 4 0.005 0 0 WNT3 chr17 53342740 53343561 822 0.31 6 0 0 0 HLF chr17 53800225 53800554 330 0.24 4 0.002 0 27868 TMEM100 chr17 55888454 55888548 95 0.29 3 0 27738 38664

chr17 60885491 60885856 366 0.27 4 0 0 0 10-Mar chr17 61553938 61554106 169 0.29 3 0 30215 0

chr17 70215735 70216332 598 0.26 3 0 93174 95292

chr17 73083876 73084329 454 0.25 6 0 0 0 SLC16A5 chr17 73584029 73584108 80 0.23 4 0.002 38816 0

chr17 77765305 77765733 429 0.25 3 0.001 3855 0

chr18 1 1751516 11751566 51 0.22 3 0.005 0 0 GNAL chr18 24130851 24131604 754 0.25 4 0.001 0 0 KCTD1 chr18 32173084 32173227 144 0.27 4 0 0 98791 DTNA chr18 55108537 55109119 583 0.25 4 0.001 0 0 ONECUT2 chr18 59560091 59560365 275 0.26 4 0 0 129 RNF152 chr18 59560394 59560495 102 0.28 3 0 89 0

chr19 2253398 2253850 453 0.27 3 0 0 0 JSRP1 chr19 2282207 2282568 362 0.22 3 0.005 0 3358 SPPL2B chr19 5338881 5339092 212 0.24 3 0.001 0 0 PTPRS chr19 16186840 16188274 1435 0.27 9 0 0 0 TPM4 chr19 18415538 18416001 464 0.22 3 0.005 1038 4488

chr19 35068555 35068710 156 0.29 3 0 0 0 SCGB1 B2P chr19 35395800 35396475 676 0.22 5 0.003 5952 0

chr19 38747355 38747378 24 0.25 3 0 7719 0

chr19 39360313 39360465 153 0.24 3 0.002 0 0 RINL chr19 39694617 39694831 215 0.24 3 0.002 0 0 SYCN chr19 40871557 40871823 267 0.24 3 0.002 0 0 PLD3 chr19 41934170 41934313 144 0.23 3 0.002 0 1 1377 B3GNT8 chr19 46379929 46380134 206 0.31 3 0 2873 0

chr19 46800054 46800602 549 0.31 8 0 0 0 RNU6-66P chr19 46800054 46800602 549 0.31 8 0 0 0 HIF3A chr19 46999274 46999307 34 0.22 3 0.006 0 0 PPP5D1 chr19 49199965 49200180 216 0.23 3 0.002 0 0 FUT2 chr19 50015527 50015780 254 0.23 3 0.003 0 751 FCGRT chr19 51416010 51416517 508 0.29 5 0 32186 0

chr19 51522454 51522641 188 0.28 4 0 0 0 KLK10 chr19 52390810 52391304 495 0.26 8 0 0 0 ZNF577 chr19 58220080 58220837 758 0.29 11 0 0 0 ZNF776 chr19 58220080 58220837 758 0.29 11 0 0 0 ZNF154 chr19 58715677 58716032 356 0.23 3 0.002 0 0 ZNF274 chr2 17699620 17699773 154 0.26 6 0 0 20382 RAD51AP2 chr2 20068702 20068906 205 0.23 3 0.003 0 0 LINC00954 chr2 26624667 26624934 268 0.23 6 0.003 0 0 DRC1 chr2 27529325 27529981 657 0.26 4 0 0 0 TRIM54 chr2 29337946 29338258 313 0.30 9 0 0 0 CLIP4 chr2 39892450 39892612 163 0.23 3 0.003 25 509

chr2 43019854 43020457 604 0.27 7 0 429083 0

chr2 43451308 43451868 561 0.27 6 0 0 0 ZFP36L2 chr2 43864913 43865055 143 0.27 3 0 0 0 PLEKHH2 chr2 45028712 45029285 574 0.22 4 0.004 28980 0

chr2 45169548 45169681 134 0.27 3 0 0 0 SIX3 chr2 45171621 45172169 549 0.28 3 0 0 0 SIX3 chr2 45176863 45177125 263 0.27 3 0 3646 0

chr2 46526785 46527098 314 0.23 3 0.004 0 0 EPAS1 chr2 50575069 50575098 30 0.23 3 0.004 0 251 NRXN1 chr2 56150255 56150478 224 0.27 4 0 0 0 EFEMP1 chr2 63283967 63284557 591 0.24 5 0.001 0 0 OTX1 chr2 63285950 63287082 1133 0.24 5 0.001 983 0

chr2 66664871 66665428 558 0.22 3 0.005 0 2532 MEIS1 chr2 68545960 68546038 79 0.21 3 0.007 0 301 CNRIP1 chr2 71205520 71206291 772 0.24 5 0 0 0 ANKRD53 chr2 74607470 74607536 67 0.23 3 0.002 0 1 1217 DCTN1 chr2 85640762 85640943 182 0.35 3 0 0 26 CAPG chr2 87016129 87016436 308 0.25 3 0.001 0 0 RMND5A chr2 87016129 87016436 308 0.25 3 0.001 0 0 CD8A chr2 96990861 96990982 122 0.24 3 0.001 79 0

chr2 99553406 99553642 237 0.29 3 0 60081 0

chr2 123418722 123419093 372 0.27 5 0 893293 905195

chr2 131595107 131595321 215 0.32 3 0 69399 0

chr2 149645394 149645798 405 0.26 4 0 0 0 KIF5C chr2 160760825 160761244 420 0.23 3 0.004 0 0 LY75-CD302 chr2 160760825 160761244 420 0.23 3 0.004 0 0 LY75 chr2 171568412 171568791 380 0.26 3 0 157 0

chr2 175208588 175208605 18 0.22 3 0.005 4272 0

chr2 176948693 176948759 67 0.23 5 0.001 8772 246

chr2 189839015 189839474 460 0.23 3 0.003 0 466683 COL3A1 chr2 190044504 190044638 135 0.23 4 0.004 0 261519 COL5A2 chr2 191044980 191045430 451 0.30 4 0 0 0 C2orf88 chr2 191045632 191045885 254 0.25 5 0 0 0 C2orf88 chr2 201450506 201450962 457 0.32 11 0 0 0 AOX1 chr2 219646481 219647360 880 0.30 5 0 0 0 CYP27A1 chr2 219846796 219847233 438 0.28 3 0 0 0 FEV chr2 220117599 2201 17945 347 0.28 7 0 0 0 TUBA4A chr2 223162875 223163033 159 0.22 3 0.004 0 0 CCDC140 chr2 223162875 223163033 159 0.22 3 0.004 0 0 PAX3 chr2 228582486 228582688 203 0.25 3 0.001 0 0 SLC19A3 chr2 228736253 228736357 105 0.26 4 0 0 0 DAW1 chr2 233498625 233499283 659 0.25 4 0 0 0 EFHD1 chr2 233741639 233741920 282 0.24 3 0.001 531 0

chr2 239140182 239140296 115 0.23 3 0.004 0 0 LOC151174 chr2 241459502 241459847 346 0.23 3 0.002 0 0 ANKMY1 chr2 241856000 241856143 144 0.23 3 0.003 37892 0

chr20 623187 623421 235 0.24 3 0.002 3846 0

chr20 642436 642782 347 0.27 3 0 0 0 SRXN1 chr20 642436 642782 347 0.27 3 0 0 0 SCRT2 chr20 3052483 3053037 555 0.24 3 0.001 0 0 OXT chr20 3220839 3220985 147 0.24 3 0.001 951 0

chr20 25129457 25129562 106 0.25 6 0 30 0

chr20 26190328 26190354 27 0.24 3 0.001 458 0

chr20 30458634 30458745 112 0.26 3 0 0 0 TTLL9 chr20 37230326 37230484 159 0.26 5 0 92 39

chr20 42875765 42875779 15 0.28 3 0 0 0 GDAP1 L1 chr20 44098223 44098724 502 0.33 8 0 0 0 WFDC2 chr20 45280237 45280288 52 0.25 3 0.001 0 67 SLC13A3 chr20 45439769 45440346 578 0.27 5 0 74783 0

chr20 50720731 50721366 636 0.29 4 0 0 0 ZFP64 chr20 61583910 61583979 70 0.22 3 0.004 4082 0

chr20 62461 159 62461539 381 0.28 4 0 0 0 ZBTB46 chr20 62693971 62694000 30 0.25 3 0 0 0 TCEA2 chr21 22369908 22370237 330 0.25 3 0.001 194481 0

chr21 34775032 34775045 14 0.27 3 0 29747 392

chr21 45148460 45148864 405 0.23 3 0.002 0 0 PDXK chr21 47717406 47718080 675 0.24 5 0 0 0 YBEY chr22 17602561 17602610 50 0.26 3 0 15799 0

chr22 28839137 28839667 531 0.35 3 0 0 235433 TTC28 chr22 31536476 31536549 74 0.23 3 0.002 6 19575

chr22 37720696 37721305 610 0.25 5 0 9306 0

chr22 45608345 45608465 121 0.22 5 0.003 0 9264 KIAA0930 chr22 4693481 1 46934981 171 0.22 3 0.005 87666 0

chr3 25469125 25469573 449 0.27 6 0 0 235983 RARB chr3 25469694 25469991 298 0.30 9 0 0 235565 RARB chr3 47050950 47051546 597 0.24 4 0.001 0 0 NBEAL2 chr3 48632484 48632672 189 0.25 5 0 0 0 COL7A1 chr3 50378425 50378527 103 0.22 3 0.005 9 0

chr3 62353504 62353894 391 0.24 3 0.001 34183 397

chr3 64253534 64253818 285 0.26 6 0 247512 0

chr3 64670459 64670907 449 0.24 5 0.001 0 180 ADAMTS9-AS2 chr3 64670459 64670907 449 0.24 5 0.001 0 180 ADAMTS9 chr3 68980539 6898101 1 473 0.30 3 0 0 0 FAM19A4 chr3 72787955 72788309 355 0.27 4 0 10118 0

chr3 87138203 87138400 198 0.27 3 0 138012 0

chr3 99594893 99595026 134 0.28 3 0 0 0 MIR548G chr3 99594893 99595026 134 0.28 3 0 0 0 FILIP1 L chr3 99594893 99595026 134 0.28 3 0 0 0 CMSS1 chr3 1 12051991 112052405 415 0.25 3 0 0 0 CD200 chr3 122296505 122296778 274 0.26 3 0 0 0 PARP15 chr3 122745092 122745560 469 0.26 3 0 0 0 SEMA5B chr3 125899878 125900108 231 0.30 7 0 0 309 ALDH1L1-AS2 chr3 125899878 125900108 231 0.30 7 0 0 309 ALDH1L1 chr3 128564782 128565090 309 0.26 6 0 31140 0

chr3 129346101 129346288 188 0.22 3 0.005 20346 0

chr3 133464867 133465180 314 0.23 3 0.002 0 0 TF chr3 134083080 134083286 207 0.31 4 0 0 0 AMOTL2 chr3 136538601 136538934 334 0.22 3 0.004 0 0 SLC35G2 chr3 138679347 138679578 232 0.30 4 0 43225 0

chr3 139258822 139258948 127 0.29 4 0 150 90

chr3 154145810 154146183 374 0.22 3 0.004 0 164 GPR149 chr3 170746029 170746291 263 0.29 6 0 167859 0

chr3 181444757 181445647 891 0.27 9 0 0 0 SOX2-OT chr3 186490344 186490777 434 0.27 4 0 10583 0

chr3 193776047 193776240 194 0.30 4 0 77690 0

chr4 779691 780336 646 0.28 3 0 0 0 CPLX1 chr4 4862770 4863016 247 0.23 3 0.002 0 528 MSX1 chr4 5710319 5710411 93 0.32 6 0 0 0 EVC2 chr4 8271391 8271507 117 0.23 3 0.002 0 0 HTRA3 chr4 9783192 9783198 7 0.27 3 0 225254 0

chr4 1 1428822 11429689 868 0.28 6 0 0 0 HS3ST1 chr4 16085077 16085716 640 0.29 8 0 0 0 PROM1 chr4 25657414 25657440 27 0.27 3 0 0 0 SLC34A2 chr4 41258910 41259044 135 0.25 3 0.001 0 0 UCHL1 chr4 41867517 41867562 46 0.32 3 0 69574 0

chr4 41869175 41869348 174 0.26 3 0 67788 0

chr4 41875193 41875784 592 0.25 4 0 61352 0

chr4 41882163 41882580 418 0.28 3 0 54556 0

chr4 41882812 41882953 142 0.23 3 0.003 54183 0

chr4 4784001 1 47840136 126 0.22 4 0.004 0 64 CORIN chr4 54960034 54960232 199 0.22 3 0.006 0 1491 PDGFRA chr4 54965829 54965904 76 0.33 3 0 0 259 PDGFRA chr4 54975677 54976184 508 0.26 4 0 0 0 PDGFRA chr4 57371589 57372597 1009 0.29 8 0 0 0 ARL9 chr4 57522493 57522795 303 0.27 4 0 0 0 HOPX chr4 74734714 74734874 161 0.24 3 0.002 14515 44

chr4 85402397 85403223 827 0.23 5 0.003 100833 0

chr4 87281281 8728151 1 231 0.26 4 0 0 233672 MAPK10 chr4 90757378 90757452 75 0.29 3 0 0 556 SNCA chr4 101 111872 101112317 446 0.27 3 0 216 374

chr4 140200723 140201100 378 0.23 3 0.002 0 0 MG ARP chr4 141488964 1414891 14 151 0.29 3 0 0 848 UCP1 chr4 154710353 154710373 21 0.22 3 0.005 83110 0

chr4 154710499 154710535 37 0.24 3 0.001 83256 0

chr4 183062301 183062576 276 0.21 3 0.007 0 0 LOC90768 chr4 188916709 188916726 18 0.26 3 0 198 0

chr4 188916865 188916943 79 0.23 4 0.002 0 0 ZFP42 chr5 1446165 1446443 279 0.29 4 0 15098 0

chr5 7849836 7850438 603 0.31 5 0 0 0 C5orf49 chr5 1 1588971 11589049 79 0.24 3 0.001 0 203449 CTNND2 chr5 42952113 42952369 257 0.25 3 0.001 62461 0

chr5 54516487 54516805 319 0.29 4 0 0 0 MCIDAS chr5 58335180 58335681 502 0.31 3 0 0 0 PDE4D chr5 59188920 59189724 805 0.23 6 0.001 0 0 PDE4D chr5 71015162 71015523 362 0.27 3 0 0 0 CARTPT chr5 72529902 72530198 297 0.25 4 0 317826 0

chr5 74907287 74908125 839 0.25 4 0.001 0 0 ANKDD1 B chr5 77253833 77253990 158 0.26 3 0 181647 0

chr5 78365647 78365691 45 0.22 3 0.004 0 0 BHMT2 chr5 78407678 78408347 670 0.25 5 0 0 41966 BHMT chr5 79330929 79331047 119 0.25 4 0 43840 0

chr5 80690205 80690225 21 0.24 3 0.001 0 0 RNU5E-1 chr5 101632310 101632341 32 0.25 5 0 56 0 chr5 1 12073348 112073538 191 0.30 10 0 0 29430 APC chr5 1 15152413 115152494 82 0.27 6 0 7 0

chr5 122620929 122621289 361 0.24 5 0.001 97183 1 15337

chr5 126205009 126205081 73 0.32 3 0 0 90779 03-Mar chr5 134735613 134735654 42 0.24 3 0.001 44249 351

chr5 137610127 137610448 322 0.29 8 0 0 0 GFRA3 chr5 139076670 139077047 378 0.25 4 0 149316 0

chr5 139525657 139525946 290 0.27 3 0 38059 0

chr5 140749735 1407501 11 377 0.24 5 0 0 0 PCDHGB3 chr5 140749735 1407501 11 377 0.24 5 0 0 0 PCDHGB2 chr5 140749735 1407501 11 377 0.24 5 0 0 0 PCDHGB1 chr5 140749735 1407501 11 377 0.24 5 0 0 0 PCDHGA5 chr5 140749735 1407501 11 377 0.24 5 0 0 0 PCDHGA4 chr5 140749735 1407501 11 377 0.24 5 0 0 0 PCDHGA3 chr5 140749735 1407501 11 377 0.24 5 0 0 0 PCDHGA2 chr5 140749735 1407501 11 377 0.24 5 0 0 0 PCDHGA1 chr5 140753415 140753449 35 0.22 3 0.005 0 205 PCDHGB3 chr5 140753415 140753449 35 0.22 3 0.005 0 205 PCDHGB2 chr5 140753415 140753449 35 0.22 3 0.005 0 205 PCDHGB1 chr5 140753415 140753449 35 0.22 3 0.005 0 205 PCDHGA5 chr5 140753415 140753449 35 0.22 3 0.005 0 205 PCDHGA4 chr5 140753415 140753449 35 0.22 3 0.005 0 205 PCDHGA3 chr5 140753415 140753449 35 0.22 3 0.005 0 205 PCDHGA2 chr5 140753415 140753449 35 0.22 3 0.005 0 205 PCDHGA1 chr5 140772182 140772286 105 0.21 3 0.008 0 99 PCDHGB3 chr5 140772182 140772286 105 0.21 3 0.008 0 99 PCDHGB2 chr5 140772182 140772286 105 0.21 3 0.008 0 99 PCDHGB1 chr5 140772182 140772286 105 0.21 3 0.008 0 99 PCDHGA7 chr5 140772182 140772286 105 0.21 3 0.008 0 99 PCDHGA6 chr5 140772182 140772286 105 0.21 3 0.008 0 99 PCDHGA5 chr5 140772182 140772286 105 0.21 3 0.008 0 99 PCDHGA4 chr5 140772182 140772286 105 0.21 3 0.008 0 99 PCDHGA3 chr5 140772182 140772286 105 0.21 3 0.008 0 99 PCDHGA2 chr5 140772182 140772286 105 0.21 3 0.008 0 99 PCDHGA1 chr5 140772182 140772286 105 0.21 3 0.008 0 99 PCDHGB4 chr5 140772182 140772286 105 0.21 3 0.008 0 99 PCDHGA8 chr5 140810051 140810161 111 0.24 6 0 0 333 PCDHGA12 chr5 140810051 140810161 111 0.24 6 0 0 333 PCDHGB7 chr5 140810051 140810161 111 0.24 6 0 0 333 PCDHGB6 chr5 140810051 140810161 111 0.24 6 0 0 333 PCDHGB5 chr5 140810051 140810161 111 0.24 6 0 0 333 PCDHGB3 chr5 140810051 140810161 111 0.24 6 0 0 333 PCDHGB2 chr5 140810051 140810161 111 0.24 6 0 0 333 PCDHGB1 chr5 140810051 140810161 111 0.24 6 0 0 333 PCDHGA11 chr5 140810051 140810161 111 0.24 6 0 0 333 PCDHGA10

chr5 140864020 140864834 815 0.26 9 0 0 0 PCDHGA3 chr5 140864020 140864834 815 0.26 9 0 0 0 PCDHGA2 chr5 140864020 140864834 815 0.26 9 0 0 0 PCDHGA1 chr5 140864020 140864834 815 0.26 9 0 0 0 PCDHGB4 chr5 140864020 140864834 815 0.26 9 0 0 0 PCDHGA8 chr5 140892677 140893101 425 0.36 3 0 128 0

chr5 141705411 141705539 129 0.29 3 0 171402 0

chr5 149535646 149535695 50 0.29 3 0 10648 10332

chr5 151066460 151066730 271 0.28 6 0 0 71262 SPARC chr5 154230141 154230438 298 0.31 5 0 0 6570 FAXDC2 chr5 156886982 156886996 15 0.23 3 0.002 0 0 ADAM 19 chr5 158524270 158524649 380 0.25 3 0.001 0 0 EBF1 chr5 169064071 169064530 460 0.29 3 0 0 0 DOCK2 chr5 172655925 172656055 131 0.23 4 0.004 64534 0

chr5 179220545 179221059 515 0.25 4 0.001 0 1549 LTC4S chr5 179220545 179221059 515 0.25 4 0.001 0 1549 MAML1 chr5 180017689 180018465 777 0.28 5 0 0 0 SCGB3A1 chr5 180018503 180018722 220 0.30 4 0 13149 0

chr6 1624978 1625574 597 0.28 5 0 0 0 GMDS chr6 2841626 2842255 630 0.28 8 0 0 0 SERPINB1 chr6 2903258 2903704 447 0.25 5 0 0 0 SERPINB9 chr6 4775132 4775222 91 0.28 3 0 0 0 CDYL chr6 10426588 10426657 70 0.27 3 0 1360 0

chr6 10881891 10882043 153 0.26 4 0 0 0 SYCP2L chr6 10881891 10882043 153 0.26 4 0 0 0 GCM2 chr6 10882238 10882336 99 0.32 5 0 0 186 SYCP2L chr6 10887023 10887185 163 0.22 4 0.005 0 0 SYCP2L chr6 21666666 21666834 169 0.24 3 0.002 0 0 CASC15 chr6 21667166 21667815 650 0.25 4 0 0 303 CASC15 chr6 26017280 26018084 805 0.26 7 0 0 2587 HIST 1 H1 A chr6 26189234 26189379 146 0.23 4 0.004 0 0 HIST 1 H4D chr6 26240782 26240939 158 0.22 3 0.006 0 0 HIST 1 H4F chr6 26271587 26271827 241 0.27 5 0 0 0 HIST1 H3G chr6 27064769 27065003 235 0.27 3 0 35091 0

chr6 27235822 27235891 70 0.31 3 0 40950 7457

chr6 28367279 28367749 471 0.25 7 0 0 0 ZSCAN12 chr6 28521796 28521837 42 0.25 3 0.001 38225 33026

chr6 29795595 29796032 438 0.23 3 0.004 1312024 0

chr6 29855302 29855636 335 0.25 6 0 1371731 0

chr6 29894619 29894820 202 0.30 6 0 1411048 0

chr6 29895016 29895074 59 0.24 3 0.002 1411445 0

chr6 29943401 29943414 14 0.21 3 0.008 1459830 988

chr6 29943455 29943480 26 0.24 4 0.001 1459884 922

chr6 29974717 29974773 57 0.23 4 0.003 1491146 0

chr6 29974810 29975080 271 0.33 12 0 1491239 0 chr6 29975366 29975427 62 0.22 3 0.004 1491795 0

chr6 30095174 30095265 92 0.28 7 0 1611603 0

chr6 30095295 30095549 255 0.25 8 0 1611724 0

chr6 30228058 30228083 26 0.27 4 o 1744487 0

chr6 30418773 30418845 73 0.22 3 0.006 1935202 0

chr6 30711073 3071 1206 134 0.26 6 0 2227502 0

chr6 30711636 3071 1802 167 0.24 7 0 2228065 0

chr6 30720261 30720491 231 0.23 4 0.003 2236690 7820

chr6 31831340 31831434 95 0.26 3 0 3347769 391

chr6 32120625 32120783 159 0.22 3 0.005 3637054 1046

chr6 32120933 32121055 123 0.23 3 0.003 3637362 774

chr6 32121156 32121261 106 0.27 6 0 3637585 568

chr6 32121368 32121433 66 0.23 4 0.004 3637797 396

chr6 32223076 32223341 266 0.26 9 0 3739505 58692

chr6 32977217 32977254 38 0.24 3 0.001 419603 1290

chr6 34984836 34984930 95 0.23 3 0.004 0 123871 ANKS1A chr6 35479628 35479910 283 0.26 3 0 0 0 TULP1 chr6 42738967 42739049 83 0.27 3 0 10740 1 1400

chr6 43211208 4321 1235 28 0.24 3 0.001 0 0 TTBK1 chr6 44187031 44187055 25 0.23 3 0.004 186 131

chr6 44310345 44310445 101 0.26 3 0 0 29146 SPATS 1 chr6 44528793 44529157 365 0.25 5 0 110631 166037

chr6 50808627 50808813 187 0.22 4 0.004 0 1829 TFAP2B chr6 50818862 50819236 375 0.22 3 0.005 3535 430

chr6 79620363 79620685 323 0.28 3 0 0 0 IRAKI BP1 chr6 1084401 18 108440339 222 0.31 3 0 44176 0

chr6 108489795 108490895 1101 0.23 6 0.001 0 0 NR2E1 chr6 1 16691382 116691863 482 0.27 5 0 0 0 DSE chr6 121758653 121758980 328 0.28 4 0 0 102630 GJA1 chr6 127835990 127836159 170 0.24 4 0.001 0 0 SOGA3 chr6 133562267 133562275 9 0.21 3 0.007 0 0 EYA4 chr6 133562479 133562494 16 0.25 4 0 0 0 EYA4 chr6 137242062 137242316 255 0.24 4 0.001 1085 0

chr6 137814078 137814971 894 0.25 5 0 0 0 OLIG3 chr6 146136371 146136749 379 0.31 4 0 0 0 LOC100507557 chr7 1270558 1270925 368 0.23 3 0.003 1728 0

chr7 1283896 1283981 86 0.28 3 0 190013 0

chr7 16505589 16505664 76 0.27 5 0 0 44323 SOSTDC1 chr7 18535232 18535767 536 0.26 6 0 0 408222 HD AC 9 chr7 19184555 19184961 407 0.24 3 0.001 0 0 FERD3L chr7 21209165 21209509 345 0.26 3 0 382656 257137

chr7 27196153 27196555 403 0.29 9 0 0 0 HOW chr7 28998195 28998346 152 0.25 3 0.001 21236 0

chr7 29185965 29186267 303 0.28 8 0 0 47437 CHN2 chr7 29185965 29186267 303 0.28 8 0 0 47437 CPVL chr7 39453532 39453704 173 0.21 3 0.007 0 0 POU6F2 chr7 39649224 39649443 220 0.26 5 0 0 0 LOC646999 chr7 45613410 45613725 316 0.25 3 0.001 13 0

chr7 49813065 49813486 422 0.27 5 0 0 0 WVC2 chr7 51538921 51539190 270 0.25 3 0 154405 82086

chr7 54956202 54956419 218 0.28 4 0 130305 0

chr7 79083445 79083509 65 0.24 4 0.001 0 0 MAGI2-AS3 chr7 92672812 92672950 139 0.24 3 0.002 206870 0

chr7 9502561 1 95025855 245 0.27 6 0 0 0 P0N1 chr7 9502561 1 95025855 245 0.27 6 0 0 0 P0N3 chr7 95026066 95026106 41 0.28 6 0 89106 0

chr7 96626151 96626659 509 0.22 3 0.005 0 4724 DLX6-AS1 chr7 97361026 97361408 383 0.32 8 0 0 0 TAC1 chr7 100464771 100465657 887 0.23 7 0 0 624 TRIP6 chr7 100488527 100489022 496 0.25 4 0 0 433 ACHE chr7 102553293 102553457 165 0.25 5 0 0 161649 LRRC17 chr7 102553293 102553457 165 0.25 5 0 0 161649 FBXL13 chr7 1 16140128 116140593 466 0.30 4 0 0 0 CAV1 chr7 1 16140128 116140593 466 0.30 4 0 0 0 CAV2 chr7 1 16164670 116164709 40 0.26 3 0 0 0 CAV1 chr7 1 17119601 117120064 464 0.27 6 0 0 51934 CFTR chr7 121956740 121956890 151 0.22 3 0.005 1587 0

chr7 127671044 127671195 152 0.23 3 0.002 0 0 SND1 chr7 127672152 127672658 507 0.29 7 0 0 0 SND1 chr7 129425330 129425858 529 0.26 5 0 44714 0

chr7 131242787 131242962 176 0.22 3 0.005 565128 0

chr7 139208852 139208979 128 0.23 3 0.002 0 0 CLEC2L chr7 143579665 143580147 483 0.42 4 0 0 1978 TCAF1 chr7 143582308 143582630 323 0.31 3 0 0 0 TCAF1 chr7 148394842 148394994 153 0.26 3 0 109469 436

chr7 149112142 149112402 261 0.32 3 0 16051 0

chr7 149389669 149389941 273 0.25 4 0 67787 0

chr7 150652808 150653195 388 0.32 7 0 0 0 KCNH2 chr7 155166290 155166554 265 0.22 3 0.005 64344 0

chr7 155255122 155255310 189 0.24 3 0.001 0 0 EN2 chr7 156797988 156798810 823 0.24 4 0.002 0 0 MNX1 chr7 156871073 156871234 162 0.27 3 0 61954 0

chr7 157361396 157362094 699 0.27 7 0 0 0 PTPRN2 chr7 157484045 157484647 603 0.27 5 0 0 0 PTPRN2 chr7 157561786 157561925 140 0.22 3 0.005 0 590 PTPRN2 chr8 10872604 10872648 45 0.22 3 0.005 0 676 XKR6 chr8 22960397 22960461 65 0.22 3 0.005 0 0 LOC254896 chr8 22960397 22960461 65 0.22 3 0.005 0 0 TNFRSF10C chr8 23563859 23563970 112 0.24 3 0.002 0 0 NKX2-6 chr8 23564025 23564591 567 0.23 6 0.003 0 0 NKX2-6 chr8 23567310 23567658 349 0.28 5 0 131775 0

chr8 41655673 41655894 222 0.27 4 0 0 0 ANK1 chr8 42356637 42356871 235 0.23 3 0.003 0 39364 SLC20A2 chr8 49468684 49468941 258 0.30 5 0 154409 0

chr8 54789207 54789978 772 0.29 4 0 0 0 RGS20 chr8 56852148 56852290 143 0.28 3 0 0 58822 LYN chr8 59058254 59058656 403 0.26 4 0 0 0 FAM110B chr8 86350390 86350592 203 0.28 4 0 0 173 CA13 chr8 104153592 104153643 52 0.21 4 0.006 0 201 BAALC chr8 105478683 105479058 376 0.24 3 0.002 0 0 DPYS chr8 120650994 120651652 659 0.30 6 0 0 193146 ENPP2 chr8 121 137879 121138232 354 0.23 3 0.002 0 100 COL14A1 chr8 140714489 140714610 122 0.26 3 0 0 0 KCNK9 chr8 144852873 144853229 357 0.22 3 0.006 19860 0

chr8 145025059 145025178 120 0.26 5 0 0 0 PLEC chr9 27528999 27529907 909 0.28 4 0 0 0 MOB3B chr9 98784231 98784351 121 0.25 3 0 193 0

chr9 1 13800909 113801337 429 0.26 3 0 0 0 LPAR1 chr9 124498633 124498961 329 0.28 3 0 0 0 DAB2IP chr9 124982087 124982834 748 0.23 3 0.004 0 0 LHX6 chr9 133320728 133320948 221 0.24 3 0.001 0 0 ASS1 chrX 13587603 13588301 699 0.29 6 0 0 0 EGFL6 chrX 21676344 21676605 262 0.24 5 0 0 0 KLHL34 chrX 25033890 25034488 599 0.26 9 0 0 0 ARX chrX 40004346 40004481 136 0.24 3 0.002 0 0 BCOR chrX 47433374 47433716 343 0.24 3 0.001 0 0 SYN1 chrX 47441605 47441779 175 0.25 3 0.001 0 7480 SYN1 chrX 47441605 47441779 175 0.25 3 0.001 0 7480 TIMP1 chrX 49022996 49023115 120 0.24 3 0.001 0 0 MAG IX chrX 50556917 50557055 139 0.25 4 0 0 0 SHROOM4 chrX 50557122 50557522 401 0.28 3 0 77 0

chrX 56258440 56258900 461 0.25 6 0 0 51 KLF8 chrX 56259040 56259373 334 0.32 4 0 0 0 KLF8 chrX 68348465 68348597 133 0.25 3 0.001 31983 0

chrX 68525613 68525883 271 0.28 3 0 199194 0

chrX 70150787 70151209 423 0.27 6 0 0 0 SLC7A3 chrX 73641881 73642885 1005 0.27 7 0 0 0 SLC16A2 chrX 100446496 100446736 241 0.31 3 0 28196 0

ARMCX5- chrX 101905837 101906288 452 0.30 5 0 0 0

GPRASP2 chrX 102000698 102000905 208 0.24 4 0.002 0 0 BHLHB9 chrX 106750120 106750612 493 0.30 5 0 205839 0

chrX 107681397 107681737 341 0.33 4 0 0 294122 COL4A6 chrX 1 19134323 119135074 752 0.26 5 0 107936 0

chrX 1 19444909 119445407 499 0.26 7 0 0 0 TMEM255A chrX 122317614 122317633 20 0.26 3 0 462 1 119 chrX 134124955 134125259 305 0.27 5 0 0 0 SMIM10

chrX 134654287 134654347 61 0.24 3 0.001 207 755

chrX 137792814 137793096 283 0.31 3 0 0 0 FGF13

chrX 142721195 142721909 715 0.26 5 0 0 0 SLITRK4

chrX 142723457 142723826 370 0.23 4 0.004 0 498 SLITRK4

chrX 153094332 153094967 636 0.29 4 0 0 0 PDZD4

chrX 154842535 154842841 307 0.31 5 0 0 0 TMLHE

Copy number changes (CNVs) in PCa correlate with DMR status

Copy number analysis identified a total of 33 segments in the tumor samples containing a minimum of five markers and one copy of loss/gain, observed in more than one tumor (Table 6). Most of these regions were located nearby coding genes. Out of these, two segments, one in chr2: 29338077 - 29338258 and the other in chr15: 45421860 - 45422325, annotating to CLIP4 and DUOX1, were most recurrently amplified among the tumors (in seven and eight samples, respectively). Comparison of the CNV and DMR lists revealed that both of these regions also show an increased level of methylation (Table 5, Figure 7 A and Figure 7B). The same incidence was also observed for regions in the promoters of KRT3 and PLEC (each amplified in three tumors), but not among other CNVs. For instance, a segment in the promoter of PNCK (amplified in three tumors) did not reveal any hypermethylation change. These results suggested that the hypermethylation pattern seen in some of the DMRs might be associated with their CNV status.

Table 6. CNV changes in prostate cancer from different tumors overlapping a total of 33 reduced genomic coordinates.

chr2 130955686 130956199 514 5 -0.3129 2 0 2 0 0 TUBA3E chr2 130955686 130956199 514 5 -0.3559 2 0 2 0 0 TUBA3E chr2 236671717 236672961 1245 5 -0.5629 2 0 2 0 342 AGAP1 chr2 236671717 236672961 1245 5 -0.5166 2 0 2 0 342 AGAP1 chr4 5710319 5710411 93 6 0.2356 0 2 2 0 0 EVC2 chr4 5710319 5710411 93 6 0.252 0 2 2 0 0 EVC2 chr4 25657365 25657440 76 6 0.2069 0 2 2 0 0 SLC34A2 chr4 25657160 25657440 281 7 0.2022 0 2 2 0 0 SLC34A2 chr6 29911004 2991 1295 292 11 0.312 0 2 2 1427433 0

chr6 29910755 2991 1265 511 16 0.2153 0 2 2 1427184 0

chr6 31276434 31276664 231 5 -0.4625 2 0 2 2792863 0

chr6 31276418 31276653 236 5 -0.3302 2 0 2 2792847 0

chr6 31324621 31325000 380 10 -0.4039 2 0 2 2841050 0

chr6 31324621 31325000 380 10 -0.4707 2 0 2 2841050 0

chr6 1 14225012 114253319 28308 5 -0.3382 2 0 2 0 38092 FLJ34503 chr6 1 14225012 114253319 28308 5 -0.4075 2 0 2 0 38092 FLJ34503 chr7 2754753 2756996 2244 5 -0.3316 2 0 2 0 1008 AMZ1 chr7 2754753 2756996 2244 5 -0.3293 2 0 2 0 1008 AMZ1 chr7 57071041 57078300 7260 10 0.2158 0 2 2 109025 0

chr7 57071676 57076951 5276 7 0.2359 0 2 2 110374 0

chr7 63057446 63088877 31432 5 -0.3413 1 1 2 416943 0

chr7 63085215 63151988 66774 5 0.2173 1 1 2 353832 0

chr7 150652864 150653195 332 6 0.2271 0 2 2 0 0 KCNH2 chr7 150652864 150653195 332 6 0.2123 0 2 2 0 0 KCNH2 chr8 216453 216788 336 5 -0.3277 2 0 2 19113 0

chr8 215923 216788 866 6 -0.3021 2 0 2 18583 0

chr8 2106183 2122339 16157 5 -0.3849 3 0 3 12802 7524 chr8 2106183 2122339 16157 5 -0.3182 3 0 3 12802 7524 chr8 2112369 2127340 14972 5 -0.3215 3 0 3 18988 2523 chr8 145025059 145025178 120 5 0.2195 0 3 3 0 0 PLEC chr8 145025059 145025178 120 5 0.212 0 3 3 0 0 PLEC chr8 145025059 145025178 120 5 0.208 0 3 3 0 0 PLEC chr10 43697817 43698141 325 5 0.2007 0 2 2 0 0 RASGEF1A chr10 43697849 43698834 986 5 0.2009 0 2 2 0 0 RASGEF1A chr10 102444675 102467056 22382 5 0.2152 0 2 2 155038 2750 chr10 102444675 102467056 22382 5 0.2468 0 2 2 155038 2750 chr10 134121577 134121712 136 5 -0.3191 2 0 2 0 0 STK32C chr10 134121577 134121712 136 5 -0.3015 2 0 2 0 0 STK32C chr1 1 22214554 22214934 381 5 -0.4099 2 0 2 0 0 AN 05 chr1 1 22214554 22214934 381 5 -0.3119 2 0 2 0 0 AN 05 chr12 3862221 3862575 355 10 0.2082 0 2 2 0 0 CRACR2A chr12 3862221 3862457 237 7 0.2053 0 2 2 0 0 CRACR2A chr12 53183930 53186067 2138 5 0.2062 0 4 4 0 0 KRT3 chr12 53183773 53186067 2295 6 0.2365 0 4 4 0 0 KRT3 chr12 53183773 53184086 314 5 0.2316 0 4 4 0 0 KRT3 chr12 53183773 53184086 314 5 0.2387 0 4 4 0 0 KRT3 chr13 96204856 96204978 123 6 0.2104 0 2 2 0 0 CLDN10 chr13 96204854 96205295 442 9 0.2404 0 2 2 0 0 CLDN10 chr15 45421998 45422095 98 6 0.2257 0 8 8 0 0 DUOXA1 chr15 45421998 45422325 328 7 0.2525 0 8 8 0 0 DUOX1 chr15 45421998 45422325 328 7 0.2525 0 8 8 0 0 DUOXA1 chr15 45421998 45422325 328 7 0.2182 0 8 8 0 0 DUOX1 chr15 45421998 45422325 328 7 0.2182 0 8 8 0 0 DUOXA1 chr15 45421998 45422325 328 7 0.226 0 8 8 0 0 DUOX1 chr15 45421998 45422325 328 7 0.226 0 8 8 0 0 DUOXA1 chr15 45421860 45422325 466 9 0.2855 0 8 8 0 0 DUOX1 chr15 45421860 45422325 466 9 0.2855 0 8 8 0 0 DUOXA1 chr15 45421998 45422325 328 7 0.2229 0 8 8 0 0 DUOX1 chr15 45421998 45422325 328 7 0.2229 0 8 8 0 0 DUOXA1 chr15 45421998 45422325 328 7 0.2023 0 8 8 0 0 DUOX1 chr15 45421998 45422325 328 7 0.2023 0 8 8 0 0 DUOXA1 chr15 45421998 45422325 328 7 0.2717 0 8 8 0 0 DUOX1 chr15 45421998 45422325 328 7 0.2717 0 8 8 0 0 DUOXA1 chr17 30592521 30593034 514 7 -0.3621 2 0 2 160 164

chr17 30592521 30593009 489 5 -0.3193 2 0 2 185 189

chr17 78808570 78809873 1304 5 -0.3047 2 0 2 0 8567 RPTOR

chr17 78808570 78809873 1304 5 -0.3107 2 0 2 0 8567 RPTOR

chr19 55035609 55038337 2729 5 0.2618 0 2 2 13708 0

chr19 55035609 55038337 2729 5 0.2483 0 2 2 13708 0

chrX 21676344 21676605 262 5 0.2095 0 3 3 0 0 KLHL34 chrX 21676344 21676605 262 5 0.2168 0 3 3 0 0 KLHL34 chrX 21676344 21676605 262 5 0.2158 0 3 3 0 0 KLHL34 chrX 48858776 48858921 146 6 -0.3813 4 0 4 100 32182

chrX 48858776 48858904 129 5 -0.3124 4 0 4 100 32182

chrX 48858688 48858832 145 5 -0.3121 4 0 4 12 32094

chrX 48858688 48858832 145 5 -0.3187 4 0 4 12 32094

chrX 152938698 152938907 210 5 0.2756 0 3 3 0 0 PNCK

chrX 152938698 152938907 210 5 0.2283 0 3 3 0 0 PNCK

chrX 152938698 152938907 210 5 0.2594 0 3 3 0 0 PNCK

DMRs in PCa are surrounded by tumor suppressor binding motifs

Analysis of 1 ,946 Homo-sapiens-specific transcription factor binding motifs from the Cis-BP database revealed that the DMR sequences rarely bind to any of these transcription factors.

Similarly, a transcription factor binding site enrichment analysis found an inverse enrichment for any of these motifs among these DMR sequences (Enrichment ratios < 1 , data not shown). We hypothesized that this might be related to the possibility that DMRs are not a direct target for regulatory elements; rather, they occur as a result of c/s-regulation by transcription factors binding to the sites around them. Therefore, we expanded the DMRs by 5 kb upstream and downstream and re-analyzed the data. We found enrichment for 25 motifs specific to 18 transcription factors (minimum fold change: 1.5, Bonferroni corrected p-value <0.01 , Figure 8). Except for a few being chromatin regulators (CGBP, MBD2, and DNMT1), all of these transcription factors were found to have tumor suppressor functionality (BRCA1 , E2F1&2&5&7, EGR1-4, FLI1 , NRF1 , TFDP2, and STAT1), or indirectly mediate the suppression of tumorigenesis and tumor suppressor activity (SP4 and ZBTB33).

A four-CoG classification model enables accurate diagnosis of PCa

To design a classification model with the ability of detecting PCa tumor status from methylation profile, we first performed feature selection from the significant PCa-related probes and then trained a logistic LASSO model with a binary outcome (tumor vs. normal). To avoid a potential bias from the copy number variations, we excluded the probes located in CNV regions. Next, we selected the non-redundant and fully differentiating probes (AUC = 1.00), which resulted in the retention of 46 CpGs. These probes were incorporated into a LASSO model, which following penalization, assigned coefficients equal to zero to 42 of the probes, dropping them out of the model. Therefore, the final model was trained using four CpGs (Figure 9A) on 16 normal samples and 31 tumors (model details in Table 7). These four CpGs are located in the first intron of OLFM1, promoter of RFX7, 12^th intron of PTPRN2, and the promoter of FLOT1, respectively (Table 7).

Table 7. Four CpGs used in the classification model.

Probe ID Chr Position Gene Enhancer DHS Island Gene location Coefficient eg 13914893 chr9 137980958 OLFM1 No No S_Shore Body 2.063 cg08857201 chr15 56536865 RFX7 No No S_Shore TSS1500 1.026 eg 04207084 chr7 157477846 PTPRN2 No No Island Body 4.717 cg07858113 chr6 30711561 IER3;FLOT1 No No Island 3'UTR;TSS1500 0.22

Model intercept: -1.687; DHS: DNase hypersensitive site; TSS1500: 1 ,500 bp away from

transcription start site

The following equation was used to calculate the decision values:

V = Inte rcep t — å Coefficie t - CpG

Where, Y is the decision value. Positive values represent tumor and negative values indicate the sample is benign.

The following equation outputs the probability of having a tumor:

To test the model, we first assessed its performance on the training data. As expected, all of the samples were assigned a correct classification of tumor vs. benign (accuracy, sensitivity, specificity, and AUC of 100%; Figure 9B). Next, to validate our algorithm, we downloaded DNA methylation array data of prostate samples publically available from GEO, and blindly supplied their methylation levels from the four CpGs to our model for classification. Of a total of 234 tumor and 76 benign prostate arrays (adjacent tissue to tumor) that we found in GEO, the algorithm correctly classified 225 as having a tumor profile and 74 as being benign, respectively. Next, we downloaded six normal prostate arrays from radical prostatectomy due to bladder cancer and ten arrays from BPH samples and supplied them to our model, all of which were classified as normal, suggesting that our algorithm can also differentiate BPH from the tumor (Figure 9C). Altogether, this analysis revealed a sensitivity of 0.96 (9 false negatives in 234 tumors), specificity of 0.98 (2 false positives among 74 adjacent benign, 6 BPH, and 10 normal), an overall accuracy of 0.97, and AUC of 0.98 for the validating dataset (Figure 9B). Among other files available from GEO were arrays from bone (n=3), lymph node (n=2), and soft tissue (n=1) with metastases from PCa, all of which were confidently predicted to have a methylation profile similar to prostate cancer. In addition, a total of 61 technical replicates of the prostate tumors were available from datasets GSE83917 and

GSE55479. Prediction scores generated for these files remained consistent with their original pairs, including the false negatives, suggesting that our model is not sensitive to technical variation. The prediction scores for all of the above array files are presented in Figure 9C and Table 8 and Table 9.

Table 8. Prediction scores generated for the validating dataset. The files presented here include all of the data used for the validation of the algorithm in addition to a total of 6 samples from tissues other than prostate containing metastasis from PCa. Duplicated array files between datasets “GSE83917” and“GSE55479” were identified and removed.

Pred.

Array file ^^rec^^' True class Array file True class

³ score ³ score

GSM1162363 6264509108_R01 C02 0.285 Benign GSM2221458_5760666013_R02C01 0.947 Cancer GSM1162364 6264509130_R04C02 0.915 Cancer GSM2221459_5760666013_R03C01 0.897 Cancer GSM1162365 6264509130_R03C02 0.918 Cancer GSM2221460_5760666013_R04C01 0.917 Cancer GSM1162369 6264509130_R06C01 0.89 Cancer GSM2221461 _5760666013_R05C01 0.909 Cancer GSM1162375 6264509130_R05C01 0.963 Cancer GSM2221462_5760666013_R01 C02 0.951 Cancer GSM1162380 6285609104_R03C02 0.435 Benign GSM2221463_5760666013_R02C02 0.904 Cancer GSM 1162381 _6285650040_R06C02 0.296 Benign GSM2221464_5760666013_R03C02 0.967 Cancer

GSM1162382_6285650050_R01 C01 0.233 Benign GSM2221465_5760666013_R04C02 0.892 Cancer GSM2221447_5765141020_R01C01 0.931 Cancer GSM2221466_5760666013_R06C02 0.905 Cancer

GSM2221448 5765141020_R02C01 0.951 Cancer GSM2221467 5760666015_R01 C01 0.931 Cancer GSM2221449 5765141020_R03C01 0.959 Cancer GSM2221468 5760666015_R05C01 0.885 Cancer GSM2221450 5765141020_R04C01 0.964 Cancer GSM2221469 5760666031 _R01 C01 0.921 Cancer GSM2221451 5765141020_R05C01 0.974 Cancer GSM2221470 5760666031 _R03C01 0.949 Cancer GSM2221452 5765141020_R02C02 0.896 Cancer GSM2221471 5760666031 _R04C01 0.805 Cancer GSM2221453 5765141020_R03C02 0.918 Cancer GSM2221476 5760666031 _R03C02 0.899 Cancer GSM2221454 5765141020_R04C02 0.93 Cancer GSM2221479_5760666032_R01 C01 0.932 Cancer GSM2221455 5765141020_R05C02 0.904 Cancer GSM2221480_5760666032_R02C01 0.873 Cancer GSM2221456 5765141020_R06C02 0.952 Cancer GSM2221481 _5760666032_R03C01 0.903 Cancer GSM2221457_5760666013_R01C01 0.939 Cancer GSM2221482_5760666032_R04C01 0.91 Cancer Pred. Pred.

Array file True class Array file True class score score

GSM2221483_5760666032_R05C01 0.959 Cancer GSM2221527 5765141040_R02C02 0.92 Cancer GSM2221484_5760666032_R06C01 0.949 Cancer GSM2221528 5765141040_R04C02 0.943 Cancer GSM2221485_5760666032_R01C02 0.919 Cancer GSM2221529 5765141040_R05C02 0.964 Cancer GSM2221486_5760666032_R02C02 0.672 Cancer GSM2221530 5765141041 _R01 C01 0.905 Cancer GSM2221487_5760666032_R03C02 0.928 Cancer GSM2221531 5765141041 _R02C01 0.299 Cancer GSM2221488_5760666032_R04C02 0.956 Cancer GSM2221532 5765141041 _R04C01 0.935 Cancer GSM2221489_5760666032_R06C02 0.939 Cancer GSM2221533 5765141041 _R01 C02 0.67 Cancer GSM2221490_5765141021_R01C01 0.857 Cancer GSM2221534 5765141041 _R02C02 0.869 Cancer GSM2221491_5765141021_R02C01 0.869 Cancer GSM2221535 5765141041 _R03C02 0.933 Cancer GSM2221492_5765141021 _R03C01 0.912 Cancer GSM2221536 5765141041 _R05C02 0.861 Cancer GSM2221493_5765141021 _R05C01 0.898 Cancer GSM2221537 5765141041 _R06C02 0.93 Cancer GSM2221494_5765141021 _R06C01 0.957 Cancer GSM2221538 5765141048_R02C01 0.943 Cancer GSM2221495_5765141021 _R03C02 0.889 Cancer GSM2221539 5765141048_R03C01 0.906 Cancer GSM2221496_5765141021 _R04C02 0.907 Cancer GSM2221553_5760666036_R01 C01 0.801 Cancer GSM2221497_5765141021_R06C02 0.968 Cancer GSM2221554_5760666036_R02C01 0.925 Cancer GSM2221498_5765141034_R02C01 0.847 Cancer GSM2221555_5760666036_R03C01 0.916 Cancer GSM2221499_5765141034_R03C01 0.913 Cancer GSM2221556_5760666036_R04C01 0.935 Cancer GSM2221500 5765141034_R04C01 0.942 Cancer GSM2221557_5760666036_R05C01 0.943 Cancer GSM2221501 5765141034_R05C01 0.928 Cancer GSM2221558_5760666049_R06C02 0.943 Cancer GSM2221502 5765141034_R06C01 0.866 Cancer GSM2221559 5760666050_R01 C01 0.953 Cancer GSM2221503 5765141034_R01 C02 0.92 Cancer GSM2221560_5760666050_R02C01 0.924 Cancer GSM2221504_5765141034_R02C02 0.93 Cancer GSM2221561 _5760666050_R03C01 0.93 Cancer GSM2221505_5765141034_R03C02 0.869 Cancer GSM2221562 3999510001 _R04C01 0.817 Cancer GSM2221506_5765141034_R05C02 0.951 Cancer GSM2221566 3999510001_R02C02 0.919 Cancer GSM2221507_5765141034_R06C02 0.924 Cancer GSM2221567 3999510001_R03C02 0.816 Cancer GSM2221508 5765141036_R01 C01 0.844 Cancer GSM2221568 3999510001_R04C02 0.869 Cancer GSM2221509 5765141036_R02C01 0.933 Cancer GSM2221604_5760666032_R05C02 0.897 Cancer GSM2221510_5765141036_R03C01 0.835 Cancer GSM2221605 5765141021 _R04C01 0.862 Cancer GSM2221511 5765141036_R04C01 0.891 Cancer GSM2221606 5765141048_R01 C01 0.749 Cancer GSM2221512 5765141036_R05C01 0.946 Cancer GSM2221607 5765141048_R04C01 0.517 Cancer GSM2221513 5765141036_R06C01 0.802 Cancer Metastasis

GSM937258_7676960077_R01C01 0.966

bone GSM2221514 5765141036_R01 C02 0.854 Cancer Metastasis

GSM937259_7676960077_R01 C02 0.873

GSM2221515 5765141036_R02C02 0.885 Cancer lymph

Metastasis GSM2221516 5765141036_R03C02 0.839 Cancer GSM937260_7676960077_R02C01 0.913

lymph GSM2221517 5765141036_R04C02 0.719 Cancer Metastasis

GSM937261 _7676960077_R02C02 0.871

soft tissue GSM2221518 5765141036_R05C02 0.946 Cancer

GSM937262_7676960077_R03C01 0.953 Cancer GSM2221519 5765141036_R06C02 0.949 Cancer

GSM937263_7676960077_R03C02 0.319 Benign GSM2221520 5765141040_R01 C01 0.932 Cancer

Metastasis GSM937264_7676960077_R04C01 0.981

GSM2221521 5765141040_R02C01 0.818 Cancer bone GSM2221522 5765141040_R03C01 0.895 Cancer GSM937265_7676960077_R04C02 0.284 Benign GSM2221523 5765141040_R04C01 0.929 Cancer GSM937266_7676960077_R05C01 0.935 Cancer GSM2221524 5765141040_R05C01 0.933 Cancer GSM937267_7676960077_R05C02 0.411 Benign

Metastasis GSM2221525 5765141040_R06C01 0.646 Cancer GSM937268_7676960077_R06C01 0.97

bone GSM2221526 5765141040_R01 C02 0.888 Cancer Pred. Pred.

Array file True class Array file True class score score

GSM937269_7676960077_R06C02 0.215 Benign GSM2041 153 0.637 Cancer

GSM2041110 0.852 Cancer GSM2041 154 0.622 Cancer

GSM2041111 0.222 Cancer GSM2041 155 0.595 Cancer

GSM2041112 0.57 Cancer GSM2041 156 0.759 Cancer

GSM2041113 0.672 Cancer GSM2041 157 0.585 Cancer

GSM2041114 0.551 Cancer GSM2041 158 0.859 Cancer

GSM2041115 0.461 Cancer GSM2041 159 0.815 Cancer

GSM2041116 0.835 Cancer GSM2041 160 0.834 Cancer

GSM2041117 0.739 Cancer GSM2041 161 0.694 Cancer

GSM2041118 0.827 Cancer GSM2041 162 0.804 Cancer

GSM2041119 0.903 Cancer GSM2041 163 0.31 Cancer

GSM2041120 0.85 Cancer GSM2041 164 0.903 Cancer

GSM2041121 0.347 Cancer GSM2041 165 0.714 Cancer

GSM2041122 0.589 Cancer GSM2041 166 0.598 Cancer

GSM2041123 0.946 Cancer GSM2041 167 0.29 Cancer

GSM2041124 0.632 Cancer GSM2041 168 0.2 Cancer

GSM2041125 0.842 Cancer GSM2041 169 0.555 Cancer

GSM2041126 0.582 Cancer GSM2041 170 0.977 Cancer

GSM2041127 0.728 Cancer GSM2041 171 0.578 Cancer

GSM2041128 0.766 Cancer GSM2041 172 0.775 Cancer

GSM2041129 0.439 Cancer GSM2041 173 0.725 Cancer

GSM2041130 0.766 Cancer GSM2041 174 0.594 Cancer

GSM2041131 0.582 Cancer GSM2041 175 0.665 Cancer

GSM2041132 0.81 Cancer GSM2041 176 0.673 Cancer

GSM2041133 0.783 Cancer GSM2041 177 0.802 Cancer

GSM2041134 0.703 Cancer GSM2041 178 0.665 Cancer

GSM2041135 0.78 Cancer GSM2041 179 0.912 Cancer

GSM2041136 0.592 Cancer GSM2041 180 0.735 Cancer

GSM2041137 0.654 Cancer GSM2041 181 0.885 Cancer

GSM2041138 0.665 Cancer GSM2041 182 0.796 Cancer

GSM2041139 0.863 Cancer GSM2041 183 0.259 Benign

GSM2041140 0.693 Cancer GSM2041 184 0.242 Benign

GSM2041141 0.678 Cancer GSM2041 185 0.299 Benign

GSM2041142 0.827 Cancer GSM2041 186 0.249 Benign

GSM2041143 0.793 Cancer GSM2041 187 0.26 Benign

GSM2041144 0.51 Cancer GSM2041 188 0.318 Benign

GSM2041145 0.51 Cancer GSM2041 189 0.277 Benign

GSM2041146 0.413 Cancer GSM2041 190 0.212 Benign

GSM2041147 0.812 Cancer GSM2041 191 0.256 Benign

GSM2041148 0.582 Cancer GSM2041 192 0.246 Benign

GSM2041149 0.795 Cancer GSM2041 193 0.222 Benign

GSM2041150 0.623 Cancer GSM2041 194 0.25 Benign

GSM2041151 0.844 Cancer GSM2041 195 0.286 Benign

GSM2041152 0.845 Cancer GSM2041 196 0.255 Benign

GSM2041234 0.206 Benign GSM 1337634 0.868 Cancer GSM2041235 0.383 Benign GSM 1337645 0.925 Cancer GSM2041236 0.282 Benign GSM 1337668 0.919 Cancer GSM2041237 0.243 Benign GSM1337673 0.966 Cancer GSM2041238 0.203 Benign GSM1337675 0.943 Cancer GSM2041239 0.181 Benign GSM 1337676 0.929 Cancer GSM2041240 0.538 Benign GSM 1337680 0.882 Cancer Pred. Pred.

Array file True class Array file True class score score

GSM 1337683 0.736 Cancer GSM1278575 0.885 Cancer GSM 1337687 0.826 Cancer GSM1278576 0.907 Cancer GSM 1337688 0.853 Cancer GSM1278577 0.795 Cancer GSM1278561 0.496 Benign GSM1278578 0.925 Cancer GSM 1278562 0.497 Benign GSM1278579 0.929 Cancer GSM 1278563 0.308 Benign GSM 1278580 0.85 Cancer GSM 1278564 0.423 Benign GSM1278581 0.861 Cancer GSM 1278565 0.295 Benign GSM 1278582 0.914 Cancer GSM 1278566 0.902 Cancer GSM 1278583 0.892 Cancer GSM 1278567 0.908 Cancer GSM 1278584 0.896 Cancer GSM 1278568 0.879 Cancer GSM 1278585 0.868 Cancer GSM 1278569 0.939 Cancer GSM 1278586 0.84 Cancer GSM 1278570 0.909 Cancer GSM 1278587 0.836 Cancer GSM1278571 0.858 Cancer GSM 1278588 0.914 Cancer GSM 1278572 0.835 Cancer GSM 1278589 0.927 Cancer GSM 1278573 0.782 Cancer GSM1278590 0.906 Cancer GSM 1278574 0.765 Cancer

Table 9. Prediction scores generated for 61 technical replicates from GSE83917 and GSE55479.

Pred. True Pred. True

Array file Array file

score class score class

GSM2221472_5760666031 _R05C01 0.906 Cancer GSM2221472 5760666031 _R05C01 0.906 Cancer GSM2221473_5760666031 _R06C01 0.881 Cancer GSM2221571 3999510044_R05C01 0.953 Cancer GSM2221474_5760666031 _R01 C02 0.908 Cancer GSM2221572 3999510044_R06C01 0.948 Cancer GSM2221475_5760666031 _R02C02 0.929 Cancer GSM2221573 3999510046_R01 C01 0.949 Cancer

GSM2221477_5760666031_R04C02 0.946 Cancer GSM2221574_3998579082_R01 C01 0.849 Cancer

GSM2221478_5760666031_R05C02 0.958 Cancer SM2221575_3998579082_R02C01 0.939 Cancer

GSM2221540_5765141058_R06C01 0.919 Cancer GSM2221576_3998579082_R03C01 0.934 Cancer

GSM2221541 _5765141058_R03C02 0.865 Cancer GSM2221578_3998579082_R04C01 0.890 Cancer GSM2221542_5765141058_R05C02 0.966 Cancer GSM2221580_3998579082_R05C01 0.892 Cancer GSM2221543_5765141058_R06C02 0.832 Cancer GSM2221583_3998579082_R01C02 0.965 Cancer GSM2221544_5765141060_R01 C01 0.936 Cancer GSM2221584_3998579082_R04C02 0.938 Cancer

GSM2221545_5765141060_R02C01 0.915 Cancer GSM2221585_3998579082_R05C02 0.934 Cancer

GSM2221546_5765141060_R03C01 0.923 Cancer GSM2221586_3998579083_R01 C01 0.920 Cancer

GSM2221547_5765141060_R04C01 0.952 Cancer GSM2221587_3998579083_R02C01 0.939 Cancer

GSM2221548_5765141060_R05C01 0.879 Cancer GSM2221588_3998579083_R04C01 0.933 Cancer

GSM2221549_5765141060_R06C01 0.956 Cancer GSM2221589_3998579083_R01C02 0.947 Cancer

GSM2221550_5765141060_R01 C02 0.942 Cancer GSM2221590_3998579083_R03C02 0.936 Cancer

GSM2221551 _5765141060_R02C02 0.932 Cancer GSM2221591_3998579083_R05C02 0.964 Cancer GSM2221552_5765141060_R03C02 0.965 Cancer GSM2221592 39985791 12_R01C01 0.901 Cancer GSM2221563_3999510001_R05C01 0.944 Cancer GSM2221593 39985791 12_R02C01 0.914 Cancer

GSM2221564_3999510001_R06C01 0.952 Cancer GSM2221594 39985791 12_R03C01 0.857 Cancer

GSM2221565_3999510001_R01 C02 0.920 Cancer GSM2221595 39985791 12_R04C01 0.809 Cancer

GSM2221569_3999510001 _R05C02 0.833 Cancer GSM2221596 39985791 12_R05C01 0.947 Cancer GSM2221570_3999510044_R04C01 0.931 Cancer GSM2221597 39985791 12_R06C01 0.943 Cancer Pred. True Pred. True

Array file Array file

score class score class

GSM2221472_5760666031 _R05C01 0.906 Cancer GSM2221472_5760666031_R05C01 0.906 Cancer GSM2221598 3998579112_R01 C02 0.767 Cancer GSM1337631 0.935 Cancer GSM2221599 3998579112_R02C02 0.886 Cancer GSM 1337691 0.932 Cancer GSM2221600 3998579112_R03C02 0.921 Cancer GSM 1337693 0.901 Cancer GSM2221601 3998579112_R04C02 0.656 Cancer GSM1337705 0.963 Cancer GSM2221602 3998579112_R06C02 0.832 Cancer GSM1337706 0.951 Cancer GSM2221603 3998579155_R04C01 0.299 Cancer* *The only misdassification was found for GSM2221603 (0.299) which is a technical replicate of another file“GSM2221531” from Table 8 with a GSM2221608_3998579082_R03C02 0.871 Cancer

similar prediction score (0.299).

GSM2221609 5765141058_R01 C02 0.867 Cancer

GSM2221610 3998579112_R05C02 0.803 Cancer

DISCUSSION

In this report, we have described DNA methylation changes in prostate cancer as compared to the adjacent benign tissue and reported a hypermethylation profile which is overrepresented in genes and interactive networks that regulate cell-cell signaling, cell communications, growth, and differentiation. Our study has revealed that the differentially methylated regions (DMRs) in PCa do not directly overlap regulatory elements; instead, they are surrounded by transcription factor binding motifs specific to tumor suppressors. And finally, we have demonstrated that by using as few as four CpGs one can accurately classify prostate specimens as malignant or benign.

Insights into the involvement of DNA methylation in PCa

A hypermethylation profile has been reported by previous DNA methylation studies of PCa, which appears to be maintained in all stages of the disease, likely due to selection pressure29’³⁵. Previous reports have also found that, in contrast to the hypermethylated CpGs that will gain further methylation during tumor progression, hypomethylation events are less likely to be maintained in the more advanced stages of the disease33. Consistent with these results, we observed that the level of hypermethylation in PCa directly correlates with the degree of tumor cellularity in the primary prostate specimens (Figure 3). The postulated link between a hypermethylation profile and cancer is a model of translational silencing of tumor suppressors by promoter hypermethylation6. Indeed, we have observed increased methylation in the promoters of several tumor suppressor genes including APC (Figure 10), a well-characterized tumor suppressor gene associated with familial adenomatous polyposis, and KLK10, which has been shown to repress proliferation and induce apoptosis in prostate cancer cells³⁶. Among other DMRs in genes involved in growth and differentiation in our study are PDE4D , encoding a signal transduction molecule with cyclic-AMP

³⁵ Geybels et al. Prostate 2015; 75( 16): 1941-50.

³⁶ Hu et al. Sci Rep 2015; 5: 17426 phosphodiesterase activity that is shown in mice to promote proliferation of prostate cancer³⁷. As well, we have observed promoter hypermethylation in estrogen receptor-related receptor gamma (ESRRG), which was also found to act as a hotspot for protein-protein interactions. Downregulation of ESRRG has been found in certain types of prostate carcinomas, and it has been shown that its increased expression can repress tumor proliferation regardless of androgen sensitivity³⁸.

Besides tumor suppressors with a potential role in cell growth and proliferation, analyses of gene-set enrichment and protein-protein interaction hotspots have revealed that methylation changes in PCa encompass a combination of biological processes extending beyond the regulation of growth to neurogenesis and cell-cell communication. The best-known involvement of neurons in cancer is perineural invasions, where tumor invades the neural tissue. Another form of neural involvement in cancer, namely neurogenesis, has been recently reported in prostate tumors as the formation of neural components, axonogenesis, and increased number of neurons³⁹. Neurogenesis has been found to correlate with both perineural invasions and poor clinical outcomes in PCa39.

Our gene enrichment analysis contains multiple GO terms related to the development of the nervous system, including brain development, axonogenesis, and neurogenesis. In parallel, these analyses provide evidence for the involvement of diverse forms of cell-cell signaling and communications, ranging from regulation of the extracellular matrix to chemotaxis and cellular response to stimuli. Among all of the genes in our results that are known to take part in these processes, the protocadherin ( PCDH) genes are mutually involved in both neurogenesis and cell cell communications. Our DMRs contain extensive regions that overlap the promoters of close to 90 PCDH gamma genes and isoforms. Various members of this cluster have been shown to be present in cell-cell adhesion, neural stroma and synapses⁴⁰, and homophilic trans-interactions⁴¹. Over-expression of PCDHs in vitro has been demonstrated to suppress Wnt signaling and to inhibit colony formations of cancer cells⁴². Limited data suggest an involvement of PCDH 8, 11, and PC in prostate cancer; however, no information is available regarding the PCDH gamma genes in PCa^43- ⁴⁵. Hypermethylation of various subtypes of PCDH gamma promoter is reported in Wilms’ tumor,

³⁷ Rahrmann et al. Cancer Res 2009;69(10):4388-97.

³⁸ Misawa et al. Front Endocrinol (Lausanne) 2015; 6: 83.

³⁹ Ayala et al. Clin Cancer Res 2008; 14(23)7593-603.

⁴⁰ Kohmura et al. Neuron 1998; 20(6): 1 137-51.

⁴¹ Schreiner et al. Proc Natl Acad Sci U S A 2010; 107(33): 14893-8.

⁴² Dallosso et al. PLoS Genet 2009;5(1 1 ):e1000745.

⁴³ Berx et al. Cold Spring Harb Perspect Biol 2009; 1 (6):a003129.

⁴⁴ Terry et al. Prostate 2006; 66(10): 1 100-13.

⁴⁵ Zhang et al. Oncol Lett 2017; 14(2): 1657-64. colorectal carcinoma, uterine leiomyosarcoma, esophageal adenocarcinoma, and Barrett’s esophagus⁴⁶.

Overall, the major biological mechanisms that can be inferred from the methylation changes in this study represent the driver events, required for the maintenance, integrity, and survival of the tumor rather than those that may initiate tumorigenesis resulting from the loss of tumor suppressor functions. Similarly, the most recurrent CNV changes in tumors were found as amplifications in the promoters of DUOX1, a NADPH oxidase involved in the maintenance of tissue homeostasis⁴⁷, as well as CLIP4, an intracellular linker protein whose knock-down has been shown to increase cell migration and viability in clear cell renal cell carcinomas⁴⁸. These two segments were also found to be hypermethylated, potentially by the expansion of the CG repeats or methylation quantitative trait loci due to CNV amplification4. Therefore, some of the hypermethylation changes we have observed in PCa might be related to the CNV status of the regions. However, the more common phenomenon that is potentially involved in the establishment of the DMRs appears to be a dysregulation following a change in tumor suppressor activity. The interesting finding that almost the entire enriched motifs nearby DMRs are specific to tumor suppressors indicates that DMRs in PCa, which mainly represent cancer driver events, are potentially generated or maintained secondary to a dysregulation in tumor suppressors’ function.

Clinical implications of the 4-CoG classification model

The current method widely in use for the diagnosis of prostate cancer is an 8-12 core needle biopsy, which is well known to encompass a high false-negative rate49. A significant number of cancer-free reports of the prostate biopsies are shown to be at risk of having an undiagnosed PCa⁴⁹. Approximately 25-50% of these men are diagnosed with PCa in a second biopsy performed within one year⁵⁰. On the other hand, a positive needle biopsy is not confidently replicable.

Serefoglu et al. have shown that a repeat PCa diagnosis can be made only in 67.8% of biopsies from post-operative prostate glands of men undergone radical prostatectomy due to PCa, using the same 12-core mapping as performed pre-operatively⁵¹. The main reason for this discrepancy is the spatiotemporal, molecular, and morphological heterogeneity of the prostate adenocarcinoma that leads to a non-uniform presentation of the tumor by the involved tissue⁵². This indicates that a significant portion of negative biopsies can contain molecular changes associated with cancer

⁴⁶ El Hajj et al. Semin Cell Dev Biol 2017; 69: 172-182

⁴⁷ Luxen et al. Cancer Res 2008; 68(4): 1037-45.

⁴⁸ Ahn et al. Oncotarget 2016;7(32):51423.

⁴⁹ Kronz et al. Am J Surg Pathol 2001 ; 25(8): 1079-85.

⁵⁰ O’dowd et al. Urology 2000; 55(4):553-8.

⁵¹ Serefoglu et al. Can Urol Assoc J 2013; 7(5-6): E293.

⁵² Cyll et al. Br J Cancer 2017; 117(3):367-375. without completely representing histological features of adenocarcinoma⁵³’⁵⁴, and thus a reliable biological marker would assign a diagnosis to a considerable number of suspicious samples undiagnosed following histopathology examination. Consistent with this, Troyer et al. was among the first to publish a report that DNA methylation markers can detect prostate cancer in

histopathologically cancer-negative prostate tissues of men who went on to have subsequently positive biopsies⁵⁵. Within a few years of this report, methylation markers in the promoters of GSTP1, APC and RASSF1 were introduced as a commercial tissue-based assay to identify patients in need of repeat biopsies⁵⁶. However, clinical validation studies of this assay have only revealed a sensitivity of 68% and a specificity of 64%⁵⁷·⁵⁸, questioning the reliability of a candidate gene approach in PCa screening. We have also observed hypermethylation to a variable extent in all these three genes (Table 1 and Table 5); however, this is not consistently observed across all specimens (Figure 10 for APC), thereby resulting in reduced sensitivity for cancer tissue

specification. As a consequence, efforts to identify DNA methylation biomarkers shifted towards a genome-wide approach for PCa. Goh et al.⁵⁹, following a genome-wide DNA methylation analysis, have proposed a 55-CpG classification model which has yielded 89.8% sensitivity and 66.7% specificity in the validation step. More recently, Kirby et al. have reported a 3-CpG model for classification of tumor samples from the adjacent benign tissues, which reached a sensitivity of 90% and specificity of 82% as measured in a validation cohort of 49 benign and 213 tumor samples29.

Here, we have further improved the classification of prostate samples by designing a 4-CpG classification model, which has revealed 100% accuracy in separating tumors from benign tissue in our internal dataset. The validation of this model using heterogeneous cohorts of 326 prostate samples from publically available resources has revealed 96% sensitivity and 98% specificity with an overall accuracy of 97% (AUC=0.98). To our knowledge, this far supersedes performance of any reported DNA methylation-based algorithm for the diagnosis of PCa. Our model is sensitive enough to detect PCa metastasis in other tissues, including bone, soft tissue, and lymph nodes (Figure 9), while it is still specific enough to discriminate benign prostate hyperplasia from the tumor. This method can be used to develop a low-cost high-throughput targeted assay for diagnosis of PCa or to complement the pathological examination of cancer-negative needle biopsies. It may also be used for confirmation of metastatic lesions outside of the prostate.

⁵³ Yang et al. Neoplasia 2013; 15(4):399-408.

4

Slater et al. Prostate cancer and prostatic diseases 2001 ; 4(2):92.

⁵⁵ Troyer et al. Cancer Epidemiol Biomarkers Prev 2009; 18(10):2717-22.

⁵⁶ Van et al. BMC Urol 2012; 12(1 ): 16.

⁵⁷ Stewart et al. J Urol 2015; 189: 1 1 10-6.

⁵⁸ Partin et al. J Urol 2014; 192: 1081-7.

⁵⁹ Goh et al. PloS One 2014;9(3):e91666. Future directions

The current classification algorithm presented in this study is designed and validated using tumor samples and normal adjacent tissues obtained from radical prostatectomy. Before this method is translated into clinical use, further computational training, validation, and clinical trials will be carried out. First, the performance of the model will be assessed on samples with diverse ranges of tumor cellularity. In the present study, we did not assess samples with tumor involvement less than 50%, and thus, the accuracy with regards to samples with lower levels of tumor cellularity will be determined. In a small subset of the tumor samples in the validation dataset, we observed scores close to the ones found in normal tissues, which might be caused by a potentially low level of tumor cellularity in them. Computationally, we can re-train the algorithm to enable the prediction of tumor cellularity as a continuous outcome. In addition, the model will be tested and re-trained as necessary on DNA obtained from needle core biopsies. In order to make this technology more broadly applicable, its accuracy will be demonstrated on limited amounts of DNA obtained from needle biopsy specimens, and the performance will be assessed across the biopsy specimens and all prostate. It will also be confirmed whether this assay can detect neoplastic transformation in specimens that appear to be normal in an initial pathological examination, but are demonstrated to harbor tumor in subsequent assessments of the same core (i.e. , false negatives).

The markers and methodology presented here could be expanded to research applications with the aim of developing novel approaches in the non-invasive screening of PCa using circulating tumor DNA. The study we have described herein reveals the power of high-throughput genomic technologies, in combination with machine learning, to increase our understanding of the biology of cancer and, at the same time, to provide us with novel, precise approaches for cancer screening and diagnosis.

The above disclosure generally describes the present invention. Although specific terms have been employed herein, such terms are intended in a descriptive sense and not for purposes of limitation.

All publications, patents and patent applications cited above are herein incorporated by reference in their entirety to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated by reference in its entirety.

Although preferred embodiments of the invention have been described herein in detail, it will be understood by those skilled in the art that variations may be made thereto without departing from the spirit of the invention or the scope of the appended claims.

Claims

1. A method for diagnosing prostate cancer in a subject, the method comprising:

2. A method for distinguishing a malignant from a benign prostate lesion in a subject, the method comprising:

3. A method for predicting tumor cellularity, the method comprising:

4. A method for detecting metastatic prostate lesions, the method comprising:

measuring the methylation level of at least one CpG locus in a sample from the subject, wherein the at least one CpG locus is selected from the loci listed in Table 1 and/or is within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides of at least one of the loci listed in Table 1 ; and determining the level of similarity between the measured methylation level and a predefined level indicative of prostate cancer, wherein a high degree of similarity between the measured methylation level and the predefined level indicates the presence or increased likelihood of a metastatic lesion.

5. The method of claim 4, wherein the sample is from a suspected metastatic site such as bone, lymph node, or soft tissue.

6. The method of any one of claims 1 to 5, wherein the at least one CpG locus comprises 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30,

31 , 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 , 42, 43, 44, 45, 46, 47, 48, 49, 50, 51 , 52, 53, 54, 55, 56,

57, 58, 59, 60, 61 , 62, 63, 64, 65, 66, 67, 68, 69, 70, 71 , 72, 73, 74, 75, 76, 77, 78, 79, 80, 81 , 82,

83, 84, 85, 86, 87, 88, 89, 90, 91 , 92, 93, 94, 95, 96, 97, 98, 99, 100, or more CpG loci.

7. The method of any one of claims 1 to 6, wherein the at least one CpG locus comprises one or more of cg13914893, cg08857201 , cg04207084, cg078581 13, cg09706021 , cg19640166, cg21264055, cg01799653, cg05326023, cg02022733, and loci within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides thereof.

8. The method of claim 7, wherein the at least one CpG locus comprises one or more of eg 13914893, cg08857201 , cg04207084, cg07858113, and loci within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides thereof.

9. The method of claim 8, wherein the at least one CpG locus comprises eg 13914893, cg08857201 , cg04207084, and cg07858113, or loci within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides thereof.

10. The method of claim 9, wherein the at least one CpG locus consists of eg 13914893, cg08857201 , cg04207084, and cg07858113, or loci within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides thereof.

1 1. The method of any one of claims 1 to 10, wherein the sample is a prostate biopsy sample.

12. The method of claim 1 1 , wherein the sample is a needle biopsy sample.

13. The method of any one of claims 1 to 10, wherein the sample is a blood sample.

14. The method of any one of claims 1 to 10, wherein the sample is a urine sample.

15. An assay comprising a probe for detecting the DNA methylation status of at least one CpG locus in a sample, wherein the at least one CpG locus is selected from the loci listed in Table 1 and/or is within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides of at least one of the loci listed in Table 1.

16. The assay of claim 15, wherein the at least one CpG locus comprises 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 , 32, 33, 34, 35,

36, 37, 38, 39, 40, 41 , 42, 43, 44, 45, 46, 47, 48, 49, 50, 51 , 52, 53, 54, 55, 56, 57, 58, 59, 60, 61 ,

62, 63, 64, 65, 66, 67, 68, 69, 70, 71 , 72, 73, 74, 75, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85, 86, 87,

88, 89, 90, 91 , 92, 93, 94, 95, 96, 97, 98, 99, 100, or more CpG loci.

17. The assay of claim 15 or 16, wherein the at least one CpG locus comprises one or more of eg 13914893, cg08857201 , cg04207084, cg07858113, cg09706021 , cg19640166, cg21264055, cg01799653, cg05326023, cg02022733, and loci within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides thereof.

18. The assay of claim 17, wherein the at least one CpG locus comprises one or more of eg 13914893, cg08857201 , cg04207084, cg07858113, and loci within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides thereof.

19. The assay of claim 18, wherein the at least one CpG locus comprises cg13914893, cg08857201 , cg04207084, and cg07858113, or loci within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides thereof.

20. The assay of claim 19, wherein the at least one CpG locus consists of eg 13914893, cg08857201 , cg04207084, and cg07858113, or loci within about 1000, 900, 800, 700, 600, 500, 400, 300, 200, or 100 nucleotides thereof.

21. The assay of any one of claims 15 to 20, wherein the assay is for diagnosing prostate cancer and/or identifying a prostate cancer metastatic lesion.

22. The assay of any one of claims 15 to 20, wherein the assay is for distinguishing between malignant and benign prostate lesions.

23. The assay of any one of claims 15 to 22, wherein the assay is a high throughput, low cost assay.

24. A method for detecting the DNA methylation status of at least one CpG locus in a sample, the method comprising contacting the sample with the assay of any one of claims 15 to 23.

25. The method of claim 24, wherein the sample is a prostate biopsy sample.

26. The method of claim 25, wherein the sample is a needle biopsy sample.

27. The method of claim 24, wherein the sample is a blood sample.

28. The method of claim 24, wherein the sample is a urine sample.

29. The method of claims 24, wherein the sample is from a site of suspected metastasis, such as from bone, lymph node, or soft tissue.

30. A method for treating prostate cancer, the method comprising diagnosing the prostate cancer according to the method of any one of claims 1 to 14 or using the assay of any one of claims 15 to 23 and, upon a positive diagnosis of prostate cancer, treating the prostate cancer.