Genome-wide analysis in 756,646 individuals provides first genetic evidence that <i>ACE2</i> expression influences COVID-19 risk and yields genetic risk scores predictive of severe disease

Abstract

SARS-CoV-2 enters host cells by binding angiotensin-converting enzyme 2 (ACE2). Through a genome-wide association study, we show that a rare variant (MAF = 0.3%, odds ratio 0.60, <i>P</i>=4.5×10^-13) that down-regulates <i>ACE2</i> expression reduces risk of COVID-19 disease, providing human genetics support for the hypothesis that ACE2 levels influence COVID-19 risk. Further, we show that common genetic variants define a risk score that predicts severe disease among COVID-19 cases.