Figure 4  Quantifying the Proportion of Causal GWAS Catalog Variants Derived from DHSs
(A) We assessed the enrichment of 1,416 independent GWAS Catalog SNPs in various genomic annotations by using GoShifter with 10,000 local shifts. We observed strong enrichment of DHSs (p < 10−4) and nominal enrichment (p < 0.05, yellow line) of H3K4me3, H3K4me1, genes, and distance to the TSS (5 and 10 kb).
(B) We performed pairwise stratified analysis for significantly enriched annotations. DHSs showed a strong residual enrichment (p < 7 × 10−4) after stratification on each of the other annotations.
(C) We generated sets of 1,416 SNPs overlapping an increasing proportion of DHSs (5% increments and 1,000 sets per increment) and determined the delta-overlap per set, yielding a delta-overlap distribution per DHS-overlap increment. We then determined the delta-overlap for the real GWAS Catalog to be 3.17 (dotted line), which corresponds to 15%–36% of loci with causal variants within DHSs (D) within the 95% confidence interval.