dna fragments were cleaned - up , end - repaired , a - tailed , and ligated with methylated paired - end adapters ( purchased from atdbio ) . see supplementary information for details . in house generated wgbs libraries were aligned using maq in bisulfite mode to the hg19/grch37 reference assembly . subsequently , cpg methylation calls were made using custom software , excluding duplicate , low quality reads as well as reads with more than 10% mismatches . methylation ratios of individual cpgs were modeled using a beta - binomial model estimating parameters from the number of methylated and total reads overlapping a given cpg , incorporating replicates . only cpgs covered by 5 reads were considered for further analysis . cpg cluster differential methylation was determined by pooling cpg level methylation differences using a random effects model . cpg cluster methylation specificity was determined using the jensen - shannon divergence of a cpg cluster s methylation level distribution across all samples and a reference distribution representing either of the two extremes : completely unmethylated or fully methylated . in silico identified cpg islands were defined by genomic regions of at least 700bp length , an cpg observed vs. expected ratio of greater than 0.6 and a gc content greater or equal than 0.5 . for the snp analysis , we obtained the ceph snp set from uscs . gwas snps were retrieved from the gwas catalog , while most of the gwas snp grouping was taken from maurano et al .. for tfbs analysis , we retrieved peak files from the encode projects and collapsed replicates . dna fragments were cleaned - up , end - repaired , a - tailed , and ligated with methylated paired - end adapters ( purchased from atdbio ) . in house generated wgbs libraries were aligned using maq in bisulfite mode to the hg19/grch37 reference assembly . subsequently , cpg methylation calls were made using custom software , excluding duplicate , low quality reads as well as reads with more than 10% mismatches . methylation ratios of individual cpgs were modeled using a beta - binomial model estimating parameters from the number of methylated and total reads overlapping a given cpg , incorporating replicates . only cpgs covered by 5 reads were considered for further analysis . cpg cluster differential methylation was determined by pooling cpg level methylation differences using a random effects model . cpg cluster methylation specificity was determined using the jensen - shannon divergence of a cpg cluster s methylation level distribution across all samples and a reference distribution representing either of the two extremes : completely unmethylated or fully methylated . in silico identified cpg islands were defined by genomic regions of at least 700bp length , an cpg observed vs. expected ratio of greater than 0.6 and a gc content greater or equal than 0.5 . for the snp analysis gwas snps were retrieved from the gwas catalog , while most of the gwas snp grouping was taken from maurano et al .. for tfbs analysis , we retrieved peak files from the encode projects and collapsed replicates .