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, P =4.5×10 -13 ) that down-regulates ACE2 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.
Competing Interests: Competing interests J.E.H., J.A.K., A.D., D.S., N.B, A.Y., A.M., R.L., E.M., X.B., D.S., F.S.P.K., J.D.B., C.O’D., A.J.M., D.A.T., A.H.L., J.M., K.W., L.G., S.E.M, H.M.K., L.D., E.S., M.J., S.B., K.S.M, W.J.S., A.R.S., A.E.L., J.M., J.O., L.H., M.N.C., J.G.R., A.B., G.R.A., and M.A.F. are current employees and/or stockholders of Regeneron Genetics Center or Regeneron Pharmaceuticals. G.H.L.R., M.V.C., D.S.P., S.C.K. A.Bal., A.R.G., S.R.M., R.P., M.Z., K.A.R., E.L.H., C.A.B. are current employees at AncestryDNA and may hold equity in AncestryDNA. The other authors declare no competing interests.