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

2021; Elsevier BV; Volume: 108; Issue: 7 Linguagem: Inglês

10.1016/j.ajhg.2021.05.017

1537-6605

Jack A. Kosmicki, Julie Horowitz, Nilanjana Banerjee, Rouel Lanche, Anthony Marcketta, Evan K. Maxwell, Xiaodong Bai, Dylan Sun, Joshua Backman, Deepika Sharma, Fabrício S. P. Kury, Hyun Min Kang, Colm O’Dushlaine, Ashish Yadav, Adam J. Mansfield, Alexander Li, Kyoko Watanabe, Lauren Gurski, Shane McCarthy, Adam E. Locke, Shareef Khalid, Sean O’Keeffe, Joelle Mbatchou, Olympe Chazara, Yunfeng Huang, Erika Kvikstad, Amanda O’Neill, Paul Nioi, Meg M. Parker, Slavé Petrovski, Heiko Runz, Joseph D. Szustakowski, Quanli Wang, Emily Wong, Aldo Córdova‐Palomera, Erin N. Smith, Sándor Szalma, Xiuwen Zheng, Sahar Esmaeeli, J. Wade Davis, Yi-Pin Lai, Xing Chen, Anne E. Justice, Joseph B. Leader, Tooraj Mirshahi, David J. Carey, Anurag Verma, Giorgio Sirugo, Marylyn D. Ritchie, Daniel J. Rader, Gundula Povysil, David B. Goldstein, Krzysztof Kiryluk, Erola Pairo‐Castineira, Konrad Rawlik, Dorota Pasko, Susan Walker, Alison Meynert, Athanasios Kousathanas, Loukas Moutsianas, Albert Tenesa, Mark J. Caulfield, Richard H. Scott, James F. Wilson, J. Kenneth Baillie, Guillaume Butler‐Laporte, Tomoko Nakanishi, Mark Lathrop, J. Brent Richards, Marcus B. Jones, Suganthi Balasubramanian, William Salerno, Alan R. Shuldiner, Jonathan Marchini, John D. Overton, Lukas Habegger, Michael Cantor, Jeffrey G. Reid, Aris Baras, Gonçalo R. Abecasis, Manuel A. R. Ferreira,

COVID-19 Clinical Research Studies

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.