One genomewide significant SNP, rs1409568, appears to be located within an active enhancer (52). This finding is consistent with a recent study that reported modest enrichment of H3K27ac marks for a variety of complex traits (e.g., Crohn’s disease)(53). Importantly, there is growing evidence that intergenic genomewide significant loci are disproportionately overrepresented in regulatory regions, such as enhancers (54–56). For example, functional partitioning of SNP-attributable heritability for 11 complex traits found that DNase1 hypersensitivity sites were 1.6- and 5.1-fold enriched in genotyped and imputed data respectively, with enhancers being the most common subcategory, representing 31.7% of total SNP heritability and 9.8-fold enrichment (54).
