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

Kosmicki, J. A.; Horowitz, J. E.; Banerjee, N.; Lanche, R.; Marcketta, A.; Maxwell, E.; Bai, X. D.; Sun, D.; Backman, J. D.; Sharma, D.; Kury, F. S. P.; Kang, H. M.; O'Dushlaine, C.; Yadav, A.; Mansfield, A. J.; Li, A. H.; Watanabe, K.; Gurski, L.; McCarthy, S. E.; Locke, A. E.; Khalid, S.; O'Keeffe, S.; Mbatchou, J.; Chazara, O.; Huang, Y. F.; Kvikstad, E.; O'Neill, A.; Nioi, P.; Parker, M. M.; Petrovski, S.; Runz, H.; Szustakowski, J. D.; Wang, Q. L.; Wong, E.; Cordova-Palomera, A.; Smith, E. N.; Szalma, S.; Zheng, X. W.; Esmaeeli, S.; Davis, J. W.; Lai, Y. P.; Chen, X.; Justice, A. E.; Leader, J. B.; Mirshahi, T.; Carey, D. J.; Verma, A.; Sirugo, G.; Ritchie, M. D.; Rader, D. J.; Povysil, G.; Goldstein, D. B.; Kiryluk, K.; Pairo-Castineira, E.; Rawlik, K.; Pasko, D.; Walker, S.; Meynert, A.; Kousathanas, A.; Moutsianas, L.; Tenesa, A.; Caulfield, M.; Scott, R.; Wilson, J. F.; Baillie, J. K.; Butler-Laporte, G.; Nakanishi, T.; Lathrop, M.; Richards, J. B.; Jones, M.; Balasubramanian, S.; Salerno, W.; Shuldiner, A. R.; Marchini, J.; Overton, J. D.; Habegger, L.; Cantor, M. N.; Reid, J. G.; Baras, A.; Abecasis, G. R.; Ferreira, M. A. R.; Regeneron Genetics, Ctr, Consortium, U. K. B. Exome Sequencing

Kosmicki, J. A.; Horowitz, J. E.; Banerjee, N.; Lanche, R.; Marcketta, A.; Maxwell, E.; Bai, X. D.; Sun, D.; Backman, J. D.; Sharma, D.; Kury, F. S. P.; Kang, H. M.; O'Dushlaine, C.; Yadav, A.; Mansfield, A. J.; Li, A. H.; Watanabe, K.; Gurski, L.; McCarthy, S. E.; Locke, A. E.; Khalid, S.; O'Keeffe, S.; Mbatchou, J.; Chazara, O.; Huang, Y. F.; Kvikstad, E.; O'Neill, A.; Nioi, P.; Parker, M. M.; Petrovski, S.; Runz, H.; Szustakowski, J. D.; Wang, Q. L.; Wong, E.; Cordova-Palomera, A.; Smith, E. N.; Szalma, S.; Zheng, X. W.; Esmaeeli, S.; Davis, J. W.; Lai, Y. P.; Chen, X.; Justice, A. E.; Leader, J. B.; Mirshahi, T.; Carey, D. J.; Verma, A.; Sirugo, G.; Ritchie, M. D.; Rader, D. J.; Povysil, G.; Goldstein, D. B.; Kiryluk, K.; Pairo-Castineira, E.; Rawlik, K.; Pasko, D.; Walker, S.; Meynert, A.; Kousathanas, A.; Moutsianas, L.; Tenesa, A.; Caulfield, M.; Scott, R.; Wilson, J. F.; Baillie, J. K.; Butler-Laporte, G.; Nakanishi, T.; Lathrop, M.; Richards, J. B.; Jones, M.; Balasubramanian, S.; Salerno, W.; Shuldiner, A. R.; Marchini, J.; Overton, J. D.; Habegger, L.; Cantor, M. N.; Reid, J. G.; Baras, A.; Abecasis, G. R.; Ferreira, M. A. R.; Regeneron Genetics, Ctr, Consortium, U. K. B. Exome Sequencing.

American Journal of Human Genetics ; 108(7):1350-1355, 2021.

Article in English | Web of Science | ID: covidwho-1312879

ABSTRACT

ABSTRACT

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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Full text: Available Collection: Databases of international organizations Database: Web of Science Language: English Journal: American Journal of Human Genetics Year: 2021 Document Type: Article

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