Epigenetic marks like DNAm have been hypothesized to underlie risk for common disease, and potentially mediating genetic risk identified from large genome-wide association studies (GWAS)30. We first examined all genetic variation previously identified in diverse GWAS using the NHGRI-EBI GWAS Catalog, which, at time of access, contains 28,870 genome-wide significant associations across 1,290 disease traits (with 15,930 unique SNPs by rs number)31. We found that 4,208 GWAS-associated SNPs for any trait was a significant DLPFC meQTL in our data (26.5% of all catalog SNPs, and 31.7% of those tested for meQTLs (Supplementary Table 8) – this enrichment of DLPFC meQTLs within GWAS-associated SNPs was highly significant (odds ratio = 1.74, χ2 p < 10−100). Interestingly, the GWAS-associated SNPs were clinically associated with 877 different disorders and/or traits affecting many tissues in the body, further suggesting that many meQTLs are not cell type-specific. We highlight examples of highly significant meQTLs where the clinical risk SNP disrupts a reference CpG dinucleotide in Figure 3 – these epigenetic effects could represent one possible mechanism by which these variants manifest risk30 (Supplementary Text 7).
