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

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...

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Autores principales: Horowitz, J. E., Kosmicki, J. A., Damask, A., Sharma, D., Roberts, G. H. L., Justice, A. E., 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., Shuldiner, A. R., Rader, D. J., 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., Ball, C. A., Baras, A., Abecasis, G. R., Ferreira, M. A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899471/
https://www.ncbi.nlm.nih.gov/pubmed/33619501
http://dx.doi.org/10.1101/2020.12.14.20248176
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author Horowitz, J. E.
Kosmicki, J. A.
Damask, A.
Sharma, D.
Roberts, G. H. L.
Justice, A. E.
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.
Shuldiner, A. R.
Rader, D. J.
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.
Ball, C. A.
Baras, A.
Abecasis, G. R.
Ferreira, M. A.
author_facet Horowitz, J. E.
Kosmicki, J. A.
Damask, A.
Sharma, D.
Roberts, G. H. L.
Justice, A. E.
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.
Shuldiner, A. R.
Rader, D. J.
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.
Ball, C. A.
Baras, A.
Abecasis, G. R.
Ferreira, M. A.
author_sort Horowitz, J. E.
collection PubMed
description 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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spelling pubmed-78994712021-02-23 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 Horowitz, J. E. Kosmicki, J. A. Damask, A. Sharma, D. Roberts, G. H. L. Justice, A. E. 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. Shuldiner, A. R. Rader, D. J. 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. Ball, C. A. Baras, A. Abecasis, G. R. Ferreira, M. A. medRxiv Article 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. Cold Spring Harbor Laboratory 2021-06-10 /pmc/articles/PMC7899471/ /pubmed/33619501 http://dx.doi.org/10.1101/2020.12.14.20248176 Text en https://creativecommons.org/licenses/by-nd/4.0/This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, and only so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Horowitz, J. E.
Kosmicki, J. A.
Damask, A.
Sharma, D.
Roberts, G. H. L.
Justice, A. E.
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.
Shuldiner, A. R.
Rader, D. J.
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.
Ball, C. A.
Baras, A.
Abecasis, G. R.
Ferreira, M. A.
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899471/
https://www.ncbi.nlm.nih.gov/pubmed/33619501
http://dx.doi.org/10.1101/2020.12.14.20248176
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