To assess how cis- and trans-eQTLs relate to known enhancer sequences, we tested for overlap between eQTLs and enhancer sequences from the Roadmap Epigenomics Consortium71. More specifically, we used chromatin states for enhancer sequences (active, genic, and weak enhancers), derived from a recent joint analysis that the Roadmap Epigenomics Consortium applied in different chromatin immunoprecipitation sequencing (ChIP-seq) data across 98 human tissues and cell lines. We included tissues that were assayed for 6 different chromatin marks (H3K4me1, H3K4me3, H3K27ac, H3K36me3, H3K27me3, and H3K9me3). We tested for enrichment of significant eQTLs at FDR ≤ 5%, using as an index eQTL SNP (eSNP) the most significantly associated SNP per gene (“max-eQTL”), which resulted in 13,137 and 851 cis- and trans-eSNPs, respectively. For each tissue or cell line, we counted the number of index eSNPs that lie within enhancer sequences respectively found in that tissue or cell line. To assess if this overlap is higher than expected by chance, we generated 1,000 sets of random SNPs matched with the index cis- and trans-eSNPs, in terms of allele frequency, gene density, distance from TSS,
