Genetic variants affecting gene expression and splicing patterns have been shown to fall within regulatory elements, providing a potential molecular basis for their effects (37–39). To assess whether the eQTLs discovered across the nine tissues were enriched in regulatory regions, we used a set of regulatory annotations from the ENCODE project (10) and the Epigenomics Roadmap project (40), including regulator-bound locations, DNase I hypersensitivity sites, and maps of histone modifications for proximal and distal regulatory regions (14). For each tissue, we chose the top significant SNP per gene from the single-tissue eQTL analysis (14,431 eQTL SNPs). Discarding SNPs that were within annotated genes resulted in 4085 intergenic eQTL SNPs, which were compared to our regulatory annotations (14). Intergenic eQTL SNPs were enriched for transcription factor-bound sites, open chromatin, promoters, and enhancers (P = 4.3 × 10−18, 2.9 × 10−8, 1.7 × 10−19, and 0.003, respectively) relative to the density of these features within a 2.5-kb window of the tested eQTLs (fig. S29 and table S11). This enrichment was even more pronounced in a subset of 91 unambiguous intergenic eQTL SNPs
