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CRISPR Screens Reveal Heart Attack-Linked Gene

Through a series of pooled CRISPR screening experiments, researchers from the Montreal Heart Institute have uncovered functional roles for a number of genetic variants that genome-wide association studies (GWAS) had previously associated with coronary artery disease (CAD). GWAS can identify genetic variants that increase the risk of various common diseases including CAD, for which more than 250 variants have been found. However, these studies cannot unambiguously pinpoint the genes responsible for the diseases. In this study, which appears in PLOS Genetics, the scientists carried out multiple CRISPR screens to test if known CAD variants impact vascular endothelial function. In total, they find 26 regions of the genome that include heart attack-associated variants and that influence the function of endothelial cells. In particular, the gene DHX38 was found to regulate vascular endothelial cell senescence, which, in turn, modulates how endothelial cells respond to stimuli that promote heart attacks.