To systematically identify the genie targets of DHSs harboring GWAS variants and thereby gain insights into disease mechanisms, we applied the approach described in (10) to the much broader range of cell and tissue types in the present study (12), and intersected the result sets with GWAS data. This analysis revealed 419 DHSs harboring GWAS variants that were strongly correlated (r > 0.7) with the promoter of a specific target gene within ±500 kb of the DHS (table S6, table S7). Among these are numerous examples of target genes that plausibly explain the disease or trait association (Table 1, fig. S7). For example, a SNP (rs385893) associated with platelet count (19) lies in a DHS tightly correlated (r = 0.97) and physically interacting with the 222 kb distant promoter of JAK2, a cytokine-activated signal transducer linked with platelet coagulation and myeloprofilerative disorders (Fig. 2A). Fully 40.8% of correlated DHS-gene pairs span >250 kb (Fig. 2B), and 79% represent pairings with distant promoters vs. those of the nearest gene (table S6, table S7). Notably, these interactions typically extend beyond the range of LD (mean r2=0.06; table S6).
