Genome-wide analysis in 756,646 individuals provides first genetic evidence that ACE2 expression influences COVID-19 risk and yields genetic risk scores predictive of severe disease
Author:
Horowitz J. E., Kosmicki J. A., Damask A., Sharma D., Roberts G. H. L., Justice A. E.ORCID, Banerjee N., Coignet M. V., Yadav A., Leader J. B., Marcketta A., Park D. S., Lanche R., Maxwell E., Knight S. C., Bai X., Guturu H., Sun D., Baltzell A., Kury F. S. P., Backman J. D., Girshick A. R., O’Dushlaine C., McCurdy S. R., Partha R., Mansfield A. J., Turissini D. A., Li A. H., Zhang M., Mbatchou J., Watanabe K., Gurski L., McCarthy S. E., Kang H. M., Dobbyn L., Stahl E., Verma A., Sirugo G., Ritchie M. D., Jones M., Balasubramanian S., Siminovitch K., Salerno W. J.ORCID, Shuldiner A. R., Rader D. J.ORCID, Mirshahi T., Locke A. E., Marchini J., Overton J. D., Carey D. J., Habegger L., Cantor M. N., Rand K. A., Hong E. L., Reid J. G.ORCID, Ball C. A., Baras A., Abecasis G. R., Ferreira M. A.,
Abstract
ABSTRACTSARS-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=4.5x10-13) 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.
Publisher
Cold Spring Harbor Laboratory
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