Reverse gene-environment interaction approach to identify variants influencing body mass index in humans

Here we derive candidate gene-environment interaction (GxE) variants from promoter-enhancer interacting regions that respond to dietary fatty acid challenge through altered chromatin accessibility in human primary adipocytes, and demonstrate that molecular genomics data produced in physiologically relevant contexts can illuminate new functional GxE mechanisms in humans and identify variants for GxE testing in large biobanks. Overall design: Assay for transposase accessible chromatin (ATAC) -seq libraries were produced from human primary preadipocytes (PAd), in vitro differntiated human adipocytes (Ad), and in vitro differentiated human adipocytes that were exposed to 200 uM palmitic acid, 200 uM oleic acid, or BSA control (all with n=3 independent replicates). Promoter Capture Hi-C libraries were produced from in vitro differentiated human white adipocytes that were exposed to 200 uM palmitic acid, 200 uM oleic acid, or BSA control (all with n=2 independent replicates).