The locations of enhancer elements coincide with DNase I hypersensitive regions of open chromatin flanked by nucleosomes marked with the mono- and/or di-methylated forms of lysine 4 at histone H3 (H3K4me1/2) [9,10]. Enhancers can be active or repressed, and each state generally correlates with the presence of additional histone marks, such as H3K27ac and H4K16ac which are associated with active chromatin, or H3K27me3 and H3K9me3 which are associated with repressed chromatin [11-14]. Active enhancers are bi-directionally transcribed and capped at their 5′ end [15,16]. Most enhancer elements are located in introns and intergenic regions, although some are exonic [17-19]. Relative to promoters, the distribution of enhancers across the epigenome is highly cell-type specific. Some of the first studies to associate GWAS variants with enhancer elements integrated genetic risk variants with regulatory element maps generated through epigenomic profiling (using chromatin immunoprecipitation combined with massively parallel DNA sequencing (ChIP-seq) and the profiling of DNase I hypersensitive sites (DHSs)) [20-22]. Two major themes emerged from these studies. First, loci with signature enhancer features (DHSs, H3K4me1, H3K27ac) are highly enriched for genetic risk variants
