To provide insights into the cellular structure of disease and potentially highlight pathogenic cell types, we explored the selective localization of GWAS SNPs within the regulatory DNA of individual cell types. We further considered the enrichment of all tested variants, not just those with genome-wide significance, and performed serial determination of the cell/tissue-selective enrichment patterns of progressively more strongly associated variants to expose collective localization within specific lineages or cell types. We used all SNPs tested in GWAS meta-analyses of two common autoimmune disorders, Crohn’s disease (26) and multiple sclerosis (MS) (27), and a common continuous physiological trait, cardiac conduction measured by the electrocardiogram QRS duration (28) (n=938,703, 2,465,832, and ~2.5M SNPs, respectively). For SNPs meeting increasingly significant P-value cutoffs, we compared the proportion of SNPs in DHSs of each cell type to the proportion of all SNPs in DHSs of the same cell type (Fig. 5). For all three studies, we observed enrichment of more weakly associated variants in regulatory DNA. This enrichment suggests that a large number of functional variants of small quantitative effect act through modulation of
