A catalog of associations between rare coding variants and COVID-19 outcomes

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Kosmicki, JA, Horowitz, JE, Banerjee, N, Lanche, R, Marcketta, A, Maxwell, E, Bai, X, Sun, D, Backman, JD, Sharma, D et al (show 70 more authors) , Kang, HM, O’Dushlaine, C, Yadav, A, Mansfield, AJ, Li, AH, Watanabe, K, Gurski, L, McCarthy, SE, Locke, AE, Khalid, S, O’Keeffe, S, Mbatchou, J, Chazara, O, Huang, Y, Kvikstad, E, O’Neill, A, Nioi, P, Parker, MM, Petrovski, S, Runz, H, Szustakowski, JD, Wang, Q, Wong, E, Cordova-Palomera, A, Smith, EN, Szalma, S, Zheng, X, Esmaeeli, S, Davis, JW, Lai, Y-P, Chen, X, Justice, AE ORCID: 0000-0002-8903-8712, Leader, JB, Mirshahi, T, Carey, DJ, Verma, A, Sirugo, G, Ritchie, MD, Rader, DJ, Povysil, G, Goldstein, DB, Kiryluk, K, Pairo-Castineira, E, Rawlik, K, Pasko, D, Walker, S, Meynert, A, Kousathanas, A, Moutsianas, L, Tenesa, A, Caulfield, M, Scott, R, Wilson, JF, Baillie, JK ORCID: 0000-0001-5258-793X, Butler-Laporte, G, Nakanishi, T, Lathrop, M, Richards, JB, Jones, M, Balasubramanian, S, Salerno, W ORCID: 0000-0003-2975-4108, Shuldiner, AR, Marchini, J, Overton, JD, Habegger, L, Cantor, MN, Reid, JG ORCID: 0000-0001-8645-4713, Baras, A, Abecasis, GR and Ferreira, MA (2020) A catalog of associations between rare coding variants and COVID-19 outcomes. [Preprint]

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Abstract

<jats:title>ABSTRACT</jats:title><jats:p>Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease-19 (COVID-19), a respiratory illness that can result in hospitalization or death. We investigated associations between rare genetic variants and seven COVID-19 outcomes in 543,213 individuals, including 8,248 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 (i) 14 interferon pathway genes in which rare deleterious variants have been reported in severe COVID-19 patients; (ii) 167 genes located in COVID-19 GWAS risk loci; or (iii) 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, with results publicly browsable at<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://rgc-covid19.regeneron.com">https://rgc-covid19.regeneron.com</jats:ext-link>.</jats:p>

Item Type:	Preprint
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User:	Symplectic Admin
Date Deposited:	30 Nov 2021 08:46
Last Modified:	18 Jan 2023 21:23
DOI:	10.1101/2020.10.28.20221804
Open Access URL:	https://www.medrxiv.org/content/10.1101/2020.10.28...
Related URLs:	Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3144195