Genetic effects on chromatin accessibility uncover mechanisms of liver gene regulation and quantitative traits

Chromatin accessibility quantitative trait locus (caQTL) studies have identified regulatory elements that may underlie genetic effects on gene expression and clinical quantitative traits. However, caQTL discovery has been limited by the sample sizes of previous studies. Here, we mapped caQTL in liver tissue from 138 human donors and identified caQTL for 35,361 regulatory elements. We identified 2,126 caQTL signals containing multiple regulatory elements, suggesting coordinated regulation of elements at these loci. CaQTL showed strong heritability enrichment and colocalization with genome-wide association study (GWAS) signals for traits relevant to liver function. We identified a colocalized caQTL at 667 GWAS signals for 17 traits, used multiple methods to predict target genes, and validated caQTL predictions at two loci using functional assays. These results demonstrate the power of caQTL to characterize gene regulation and predict regulatory mechanisms at GWAS loci.