To further understand the mechanisms underlying sQTLs, we assessed the overlap of sQTLs with SNPs influencing epigenomic marks (xQTLs) such as DNA methylation (mQTL) and histone H3 acetylation on lysine 9 (H3K9Ac, haQTL)29 that are available from the same DLPFC samples. Indeed, we found that such xQTLs29 are significantly enriched among sQTLs when compared to randomly selected, matched SNPs (Kolmogorov–Smirnov test P < 0.001): of the lead sQTL, 9% (578) were also associated with an haQTL, and 19% (1246) were also an mQTL (Fig. 3d). This suggests that there an important subset of genetic variants co-influences splicing, methylation levels, and histone modifications. In a complementary analysis, we found significant sharing of sQTL SNPs among SNPs that also influence histone (π1 = 0.74) or methylation (π1 = 0.82). These overlaps suggest that there is a contribution of epigenomic regulation in splicing.
