We used data from ENCODE and the Roadmap Epigenomics Project10,22–24 to assess whether sites characterized by genotype-associated DNA methylation co-localize with genomic regions associated with markers of transcriptional activity. We observed an enrichment of fetal brain mQTLs in genomic regions characterized by ChIP-seq peaks for repressive histone modifications in fetal brain – for example, H3K9me3 (relative enrichment = 1.43, P = 0.00107) and H3K27me3 (relative enrichment = 1.16, P = 0.000144) - and a significant depletion of fetal brain mQTLs in genomic regions defined by ChIP-seq peaks for histone modifications associated with active transcription – for example, H3K4me1 (relative enrichment = 0.828, P = 6.55×10−8) and H3K36me3 (relative enrichment = 0.543, P = 1.39×10−15 (Supplementary Table 6). Fetal brain mQTLs were found to be significantly enriched in regions of open chromatin indicated by DNase1 hypersensitivity sites (DHSs) identified in the adult human brain (Supplementary Table 7), consistent with the observation that intermediately methylated domains, one potential consequence of allele-specific DNA methylation, are enriched in DHSs25. We also identified a significant enrichment of genotype-associated DNA methylation sites overlapping annotated transcription factor
