Pan-ancestry exome-wide association analyses of COVID-19 outcomes in 586,157 individuals

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a respiratory illness that can result in hospitalization or death. We used exome sequence data to investigate associations between rare genetic variants and seven COVID-19 outcomes in 586,157 ind...

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Published in:American journal of human genetics Vol. 108; no. 7; p. 1350
Main Authors: Kosmicki, Jack A, Horowitz, Julie E, Banerjee, Nilanjana, Lanche, Rouel, Marcketta, Anthony, Maxwell, Evan, Bai, Xiaodong, Sun, Dylan, Backman, Joshua D, Sharma, Deepika, Kury, Fabricio S P, Kang, Hyun M, O'Dushlaine, Colm, Yadav, Ashish, Mansfield, Adam J, Li, Alexander H, Watanabe, Kyoko, Gurski, Lauren, McCarthy, Shane E, Locke, Adam E, Khalid, Shareef, O'Keeffe, Sean, Mbatchou, Joelle, Chazara, Olympe, Huang, Yunfeng, Kvikstad, Erika, O'Neill, Amanda, Nioi, Paul, Parker, Meg M, Petrovski, Slavé, Runz, Heiko, Szustakowski, Joseph D, Wang, Quanli, Wong, Emily, Cordova-Palomera, Aldo, Smith, Erin N, Szalma, Sandor, Zheng, Xiuwen, Esmaeeli, Sahar, Davis, Justin W, Lai, Yi-Pin, Chen, Xing, Justice, Anne E, Leader, Joseph B, Mirshahi, Tooraj, Carey, David J, Verma, Anurag, Sirugo, Giorgio, Ritchie, Marylyn D, Rader, Daniel J, Povysil, Gundula, Goldstein, David B, Kiryluk, Krzysztof, Pairo-Castineira, Erola, Rawlik, Konrad, Pasko, Dorota, Walker, Susan, Meynert, Alison, Kousathanas, Athanasios, Moutsianas, Loukas, Tenesa, Albert, Caulfield, Mark, Scott, Richard, Wilson, James F, Baillie, J Kenneth, Butler-Laporte, Guillaume, Nakanishi, Tomoko, Lathrop, Mark, Richards, J Brent, Jones, Marcus, Balasubramanian, Suganthi, Salerno, William, Shuldiner, Alan R, Marchini, Jonathan, Overton, John D, Habegger, Lukas, Cantor, Michael N, Reid, Jeffrey G, Baras, Aris, Abecasis, Goncalo R, Ferreira, Manuel A R
Format: Journal Article
Language:English
Published: United States 01.07.2021
Subjects:
COVID-19 - diagnosis
COVID-19 - genetics
COVID-19 - immunology
COVID-19 - therapy
Exome - genetics
Exome Sequencing
Female
Genetic Predisposition to Disease
Hospitalization - statistics & numerical data
Humans
Interferons - genetics
Male
Prognosis
Sample Size
SARS-CoV-2
COVID-19
rare variants
SARS-CoV-2
exome sequencing
genetics
association
TLR7
ZC3HAV1
burden
ISSN:1537-6605, 1537-6605
Online Access:Get more information
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Summary:Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a respiratory illness that can result in hospitalization or death. We used exome sequence data to investigate associations between rare genetic variants and seven COVID-19 outcomes in 586,157 individuals, including 20,952 with COVID-19. After accounting for multiple testing, we did not identify any clear associations with rare variants either exome wide or when specifically focusing on (1) 13 interferon pathway genes in which rare deleterious variants have been reported in individuals with severe COVID-19, (2) 281 genes located in susceptibility loci identified by the COVID-19 Host Genetics Initiative, or (3) 32 additional genes of immunologic relevance and/or therapeutic potential. Our analyses indicate there are no significant associations with rare protein-coding variants with detectable effect sizes at our current sample sizes. Analyses will be updated as additional data become available, and results are publicly available through the Regeneron Genetics Center COVID-19 Results Browser.
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ISSN:1537-6605
1537-6605
DOI:10.1016/j.ajhg.2021.05.017