Functional variants that alter transcription factor recognition sequences frequently affect local chromatin structure. At heterozygous SNPs altering transcription factor recognition sequences, altered nuclease accessibility of the chromatin template manifests as an imbalance in the fraction of reads obtained from each allele (20, 21). As the concentration of sequence reads and highly overlapping read coverage results in an effective re-sequencing of DHSs, we were able both to detect cell types heterozygous for common SNPs and to quantify the relative proportions of reads from each allele across all cell types (12). This imbalance is indicative of the functional effect of a particular allele on local chromatin state. We detected 584 heterozygous GWAS SNPs with sufficient sequencing coverage, of which 120 showed significant allelic imbalance in chromatin state (at FDR 5%). We identified sites where regulatory variants were associated with allelic chromatin states, 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
