tetano
Editor, Senior Moderator
Am J Hum Genet
. 2021 Jun 3;S0002-9297(21)00222-6.
doi: 10.1016/j.ajhg.2021.05.017. Online ahead of print.
Pan-ancestry exome-wide association analyses of COVID-19 outcomes in 586,157 individuals
Jack A Kosmicki[SUP] 1 [/SUP], Julie E Horowitz[SUP] 1 [/SUP], Nilanjana Banerjee[SUP] 1 [/SUP], Rouel Lanche[SUP] 1 [/SUP], Anthony Marcketta[SUP] 1 [/SUP], Evan Maxwell[SUP] 1 [/SUP], Xiaodong Bai[SUP] 1 [/SUP], Dylan Sun[SUP] 1 [/SUP], Joshua D Backman[SUP] 1 [/SUP], Deepika Sharma[SUP] 1 [/SUP], Fabricio S P Kury[SUP] 1 [/SUP], Hyun M Kang[SUP] 1 [/SUP], Colm O'Dushlaine[SUP] 1 [/SUP], Ashish Yadav[SUP] 1 [/SUP], Adam J Mansfield[SUP] 1 [/SUP], Alexander H Li[SUP] 1 [/SUP], Kyoko Watanabe[SUP] 1 [/SUP], Lauren Gurski[SUP] 1 [/SUP], Shane E McCarthy[SUP] 1 [/SUP], Adam E Locke[SUP] 1 [/SUP], Shareef Khalid[SUP] 1 [/SUP], Sean O'Keeffe[SUP] 1 [/SUP], Joelle Mbatchou[SUP] 1 [/SUP], Olympe Chazara[SUP] 2 [/SUP], Yunfeng Huang[SUP] 3 [/SUP], Erika Kvikstad[SUP] 4 [/SUP], Amanda O'Neill[SUP] 2 [/SUP], Paul Nioi[SUP] 5 [/SUP], Meg M Parker[SUP] 5 [/SUP], Slavé Petrovski[SUP] 2 [/SUP], Heiko Runz[SUP] 3 [/SUP], Joseph D Szustakowski[SUP] 4 [/SUP], Quanli Wang[SUP] 2 [/SUP], Emily Wong[SUP] 6 [/SUP], Aldo Cordova-Palomera[SUP] 6 [/SUP], Erin N Smith[SUP] 6 [/SUP], Sandor Szalma[SUP] 6 [/SUP], Xiuwen Zheng[SUP] 7 [/SUP], Sahar Esmaeeli[SUP] 7 [/SUP], Justin W Davis[SUP] 7 [/SUP], Yi-Pin Lai[SUP] 8 [/SUP], Xing Chen[SUP] 8 [/SUP], Anne E Justice[SUP] 9 [/SUP], Joseph B Leader[SUP] 9 [/SUP], Tooraj Mirshahi[SUP] 9 [/SUP], David J Carey[SUP] 9 [/SUP], Anurag Verma[SUP] 10 [/SUP], Giorgio Sirugo[SUP] 10 [/SUP], Marylyn D Ritchie[SUP] 10 [/SUP], Daniel J Rader[SUP] 10 [/SUP], Gundula Povysil[SUP] 11 [/SUP], David B Goldstein[SUP] 12 [/SUP], Krzysztof Kiryluk[SUP] 13 [/SUP], Erola Pairo-Castineira[SUP] 14 [/SUP], Konrad Rawlik[SUP] 15 [/SUP], Dorota Pasko[SUP] 16 [/SUP], Susan Walker[SUP] 16 [/SUP], Alison Meynert[SUP] 17 [/SUP], Athanasios Kousathanas[SUP] 16 [/SUP], Loukas Moutsianas[SUP] 16 [/SUP], Albert Tenesa[SUP] 18 [/SUP], Mark Caulfield[SUP] 19 [/SUP], Richard Scott[SUP] 20 [/SUP], James F Wilson[SUP] 21 [/SUP], J Kenneth Baillie[SUP] 22 [/SUP], Guillaume Butler-Laporte[SUP] 23 [/SUP], Tomoko Nakanishi[SUP] 24 [/SUP], Mark Lathrop[SUP] 25 [/SUP], J Brent Richards[SUP] 26 [/SUP], Regeneron Genetics Center; UKB Exome Sequencing Consortium; Marcus Jones[SUP] 1 [/SUP], Suganthi Balasubramanian[SUP] 1 [/SUP], William Salerno[SUP] 1 [/SUP], Alan R Shuldiner[SUP] 1 [/SUP], Jonathan Marchini[SUP] 1 [/SUP], John D Overton[SUP] 1 [/SUP], Lukas Habegger[SUP] 1 [/SUP], Michael N Cantor[SUP] 1 [/SUP], Jeffrey G Reid[SUP] 1 [/SUP], Aris Baras[SUP] 1 [/SUP], Goncalo R Abecasis[SUP] 27 [/SUP], Manuel A R Ferreira[SUP] 28 [/SUP]
Affiliations
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.
Keywords: COVID-19; SARS-CoV-2; TLR7; ZC3HAV1; association; burden; exome sequencing; genetics; rare variants.
. 2021 Jun 3;S0002-9297(21)00222-6.
doi: 10.1016/j.ajhg.2021.05.017. Online ahead of print.
Pan-ancestry exome-wide association analyses of COVID-19 outcomes in 586,157 individuals
Jack A Kosmicki[SUP] 1 [/SUP], Julie E Horowitz[SUP] 1 [/SUP], Nilanjana Banerjee[SUP] 1 [/SUP], Rouel Lanche[SUP] 1 [/SUP], Anthony Marcketta[SUP] 1 [/SUP], Evan Maxwell[SUP] 1 [/SUP], Xiaodong Bai[SUP] 1 [/SUP], Dylan Sun[SUP] 1 [/SUP], Joshua D Backman[SUP] 1 [/SUP], Deepika Sharma[SUP] 1 [/SUP], Fabricio S P Kury[SUP] 1 [/SUP], Hyun M Kang[SUP] 1 [/SUP], Colm O'Dushlaine[SUP] 1 [/SUP], Ashish Yadav[SUP] 1 [/SUP], Adam J Mansfield[SUP] 1 [/SUP], Alexander H Li[SUP] 1 [/SUP], Kyoko Watanabe[SUP] 1 [/SUP], Lauren Gurski[SUP] 1 [/SUP], Shane E McCarthy[SUP] 1 [/SUP], Adam E Locke[SUP] 1 [/SUP], Shareef Khalid[SUP] 1 [/SUP], Sean O'Keeffe[SUP] 1 [/SUP], Joelle Mbatchou[SUP] 1 [/SUP], Olympe Chazara[SUP] 2 [/SUP], Yunfeng Huang[SUP] 3 [/SUP], Erika Kvikstad[SUP] 4 [/SUP], Amanda O'Neill[SUP] 2 [/SUP], Paul Nioi[SUP] 5 [/SUP], Meg M Parker[SUP] 5 [/SUP], Slavé Petrovski[SUP] 2 [/SUP], Heiko Runz[SUP] 3 [/SUP], Joseph D Szustakowski[SUP] 4 [/SUP], Quanli Wang[SUP] 2 [/SUP], Emily Wong[SUP] 6 [/SUP], Aldo Cordova-Palomera[SUP] 6 [/SUP], Erin N Smith[SUP] 6 [/SUP], Sandor Szalma[SUP] 6 [/SUP], Xiuwen Zheng[SUP] 7 [/SUP], Sahar Esmaeeli[SUP] 7 [/SUP], Justin W Davis[SUP] 7 [/SUP], Yi-Pin Lai[SUP] 8 [/SUP], Xing Chen[SUP] 8 [/SUP], Anne E Justice[SUP] 9 [/SUP], Joseph B Leader[SUP] 9 [/SUP], Tooraj Mirshahi[SUP] 9 [/SUP], David J Carey[SUP] 9 [/SUP], Anurag Verma[SUP] 10 [/SUP], Giorgio Sirugo[SUP] 10 [/SUP], Marylyn D Ritchie[SUP] 10 [/SUP], Daniel J Rader[SUP] 10 [/SUP], Gundula Povysil[SUP] 11 [/SUP], David B Goldstein[SUP] 12 [/SUP], Krzysztof Kiryluk[SUP] 13 [/SUP], Erola Pairo-Castineira[SUP] 14 [/SUP], Konrad Rawlik[SUP] 15 [/SUP], Dorota Pasko[SUP] 16 [/SUP], Susan Walker[SUP] 16 [/SUP], Alison Meynert[SUP] 17 [/SUP], Athanasios Kousathanas[SUP] 16 [/SUP], Loukas Moutsianas[SUP] 16 [/SUP], Albert Tenesa[SUP] 18 [/SUP], Mark Caulfield[SUP] 19 [/SUP], Richard Scott[SUP] 20 [/SUP], James F Wilson[SUP] 21 [/SUP], J Kenneth Baillie[SUP] 22 [/SUP], Guillaume Butler-Laporte[SUP] 23 [/SUP], Tomoko Nakanishi[SUP] 24 [/SUP], Mark Lathrop[SUP] 25 [/SUP], J Brent Richards[SUP] 26 [/SUP], Regeneron Genetics Center; UKB Exome Sequencing Consortium; Marcus Jones[SUP] 1 [/SUP], Suganthi Balasubramanian[SUP] 1 [/SUP], William Salerno[SUP] 1 [/SUP], Alan R Shuldiner[SUP] 1 [/SUP], Jonathan Marchini[SUP] 1 [/SUP], John D Overton[SUP] 1 [/SUP], Lukas Habegger[SUP] 1 [/SUP], Michael N Cantor[SUP] 1 [/SUP], Jeffrey G Reid[SUP] 1 [/SUP], Aris Baras[SUP] 1 [/SUP], Goncalo R Abecasis[SUP] 27 [/SUP], Manuel A R Ferreira[SUP] 28 [/SUP]
Affiliations
- PMID: 34115965
- PMCID: PMC8173480
- DOI: 10.1016/j.ajhg.2021.05.017
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.
Keywords: COVID-19; SARS-CoV-2; TLR7; ZC3HAV1; association; burden; exome sequencing; genetics; rare variants.