with the predicted higher-affinity allele exhibiting higher accessibility (Fig. 2C). In nearly 50% of cases, the magnitude of imbalance was >2:1 (fig. S9). The GWAS SNPs were the sole local sequence difference between haplotypes, indicating that disease-associated variants are responsible for modulating local chromatin accessibility. Further, at sites with very high sequencing depth (>200x), 38.7% (53/137) show significant allelic imbalance (FDR < 5%). As sensitivity to detect allelic imbalance is governed by sequencing depth, this suggests that nearly 40% of GWAS variants in similarly-sequenced DHSs would be expected to show allelic imbalance.
