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.

J E Horowitz, J A Kosmicki, A Damask,D Sharma,G H L Roberts,A E Justice, N Banerjee, M V Coignet,A Yadav, J B Leader, A Marcketta, D S Park, R Lanche, E Maxwell, S C Knight, X Bai,H Guturu, D Sun, A Baltzell, F S P Kury,J D Backman,A R Girshick, C O'Dushlaine, S R McCurdy,R Partha, A J Mansfield, D A Turissini,A H Li, M Zhang,J Mbatchou, K Watanabe, L Gurski, S E McCarthy, H M Kang, L Dobbyn,E Stahl, A Verma, G Sirugo, ,M D Ritchie,M Jones, S Balasubramanian, K Siminovitch,W J Salerno,A R Shuldiner,D J Rader, T Mirshahi, A E Locke,J Marchini,J D Overton,D J Carey, L Habegger,M N Cantor,K A Rand, E L Hong, J G Reid,C A Ball, A Baras,G R Abecasis,M A Ferreira

medRxiv : the preprint server for health sciences（2021）

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摘要

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.

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关键词

genetic risk scores predictive,first genetic evidence,disease,genome-wide

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