The hypothesis that most GWA discovered loci will have an underlying common variant that impacts regulation of gene expression was recently tested by Stamatoyannopoulos and colleagues (69). They first examined regions of the genome where the chromatin is unpacked and available for binding transcription factors, as marked by hypersensitivity to cleavage by DNase I enzymes. The next step was to look for an enrichment of disease and trait-associated loci from GWA studies in these DNase hypersensitive regions. The authors identified a 40% enrichment of these disease- and trait-associated SNPs from GWAS (P < 10−55) in these DNase hypersensitive regions indicating regulatory function. We also assessed, as a simple proxy for function, the distance to the nearest gene for three categories of variants; those that show association from GWA studies, those examined in GWA studies, and HapMap SNPs (Figure 1B). For the first category, 90% of variants are within 87 kb of a gene, however, for the third category, 90% of variants are within 367 kb of a gene.
