We next integrated the genomic elements described above into a regulatory network. We first processed a Hi-C dataset for adult brain in the same reference samples used for enhancer identification, providing a physical basis for interactions between enhancers and promoters (Fig. 5A and table S8) (13, 21). In total, we identified 2735 topologically associating domains (TADs) and ~90,000 enhancer-promoter interactions (fig. S36). As expected, ~75% of enhancer-promoter interactions occurred within the same TAD, and genes with more enhancers tended to have higher expression (Fig. 5B and fig. S36). We integrated the Hi-C data with QTLs; surprisingly, QTLs involving SNPs distal to eGenes but linked by Hi-C interactions showed significantly stronger associations (as indicated by the QTL P value) than those with SNPs directly in the eGene promoter or exons (Fig. 5C and fig. S37).
