TY - JOUR
T1 - Genomewide association study of severe covid-19 with respiratory failure
AU - The Severe Covid-19 GWAS Group
AU - Ellinghaus, David
AU - Degenhardt, Frauke
AU - Bujanda, Luis
AU - Buti, Maria
AU - Albillos, Agustín
AU - Invernizzi, Pietro
AU - Fernández, Javier
AU - Prati, Daniele
AU - Baselli, Guido
AU - Asselta, Rosanna
AU - Grimsrud, Marit M.
AU - Milani, Chiara
AU - Zanella, Alberto
AU - Bandera, Alessandra
AU - Protti, Alessandro
AU - Aghemo, Alessio
AU - Lleo, Ana
AU - Gori, Andrea
AU - Latiano, Anna
AU - Fracanzani, Anna Ludovica
AU - Pesenti, Antonio
AU - Voza, Antonio
AU - Paccapelo, Cinzia
AU - Angelini, Claudio
AU - Ceriotti, Ferruccio
AU - Martinelli-Boneschi, Filippo
AU - Peyvandi, Flora
AU - Blasi, Francesco
AU - Grasselli, Giacomo
AU - Costantino, Giorgio
AU - Cardamone, Giulia
AU - Terranova, Leonardo
AU - Santoro, Luigi
AU - Scudeller, Luigia
AU - Carrabba, Maria
AU - Cecconi, Maurizio
AU - Ciccarelli, Michele
AU - Miozzo, Monica
AU - Montano, Nicola
AU - Palmieri, Orazio
AU - Preatoni, Paoletta
AU - Tentorio, Paolo
AU - Badalamenti, Salvatore
AU - Pelusi, Serena
AU - Aliberti, Stefano
AU - Monzani, Valter
AU - Rimoldi, Valeria
AU - Bosari, Silvano
AU - Duga, Stefano
AU - Valenti, Luca
N1 - Funding Information:
Supported by a philanthropic donation from Stein Erik Hagen and Canica; by a grant from the Deutsche Forschungsgemein-schaft Cluster of Excellence “Precision Medicine in Chronic Inflammation” (EXC2167); by a Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Covid-19 Biobank grant (to Dr. Valenti); by grants from the Italian Ministry of Health (RF-2016-02364358, to Dr. Valenti) and Ministero dell’Istruzione, dell’Università e della Ricerca project “Dipartimenti di Eccel-lenza 2018–2022” (D15D18000410001 to the Department of Medical Sciences, University of Turin; by a grant from the Spanish Ministry of Science and Innovation JdC fellowship (IJC2018-035131-I, to Dr. Acosta-Herrera); and by the GCAT Cession Research Project PI-2020-01. HLA typing was performed and supported by the Stefan-Morsch-Stiftung.
Publisher Copyright:
Copyright © 2020 Massachusetts Medical Society.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/10/15
Y1 - 2020/10/15
N2 - BACKGROUND There is considerable variation in disease behavior among patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19). Genomewide association analysis may allow for the identification of potential genetic factors involved in the development of Covid-19. METHODS We conducted a genomewide association study involving 1980 patients with Covid-19 and severe disease (defined as respiratory failure) at seven hospitals in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe. After quality control and the exclusion of population outliers, 835 patients and 1255 control participants from Italy and 775 patients and 950 control participants from Spain were included in the final analysis. In total, we analyzed 8,582,968 single-nucleotide polymorphisms and conducted a meta-analysis of the two case–control panels. RESULTS We detected cross-replicating associations with rs11385942 at locus 3p21.31 and with rs657152 at locus 9q34.2, which were significant at the genomewide level (P<5×10−8) in the meta-analysis of the two case–control panels (odds ratio, 1.77; 95% confidence interval [CI], 1.48 to 2.11; P=1.15×10−10; and odds ratio, 1.32; 95% CI, 1.20 to 1.47; P=4.95×10−8, respectively). At locus 3p21.31, the association signal spanned the genes SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1. The association signal at locus 9q34.2 coincided with the ABO blood group locus; in this cohort, a blood-group–specific analysis showed a higher risk in blood group A than in other blood groups (odds ratio, 1.45; 95% CI, 1.20 to 1.75; P=1.48×10−4) and a protective effect in blood group O as compared with other blood groups (odds ratio, 0.65; 95% CI, 0.53 to 0.79; P=1.06×10−5). CONCLUSIONS We identified a 3p21.31 gene cluster as a genetic susceptibility locus in patients with Covid-19 with respiratory failure and confirmed a potential involvement of the ABO blood-group system.
AB - BACKGROUND There is considerable variation in disease behavior among patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19). Genomewide association analysis may allow for the identification of potential genetic factors involved in the development of Covid-19. METHODS We conducted a genomewide association study involving 1980 patients with Covid-19 and severe disease (defined as respiratory failure) at seven hospitals in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe. After quality control and the exclusion of population outliers, 835 patients and 1255 control participants from Italy and 775 patients and 950 control participants from Spain were included in the final analysis. In total, we analyzed 8,582,968 single-nucleotide polymorphisms and conducted a meta-analysis of the two case–control panels. RESULTS We detected cross-replicating associations with rs11385942 at locus 3p21.31 and with rs657152 at locus 9q34.2, which were significant at the genomewide level (P<5×10−8) in the meta-analysis of the two case–control panels (odds ratio, 1.77; 95% confidence interval [CI], 1.48 to 2.11; P=1.15×10−10; and odds ratio, 1.32; 95% CI, 1.20 to 1.47; P=4.95×10−8, respectively). At locus 3p21.31, the association signal spanned the genes SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1. The association signal at locus 9q34.2 coincided with the ABO blood group locus; in this cohort, a blood-group–specific analysis showed a higher risk in blood group A than in other blood groups (odds ratio, 1.45; 95% CI, 1.20 to 1.75; P=1.48×10−4) and a protective effect in blood group O as compared with other blood groups (odds ratio, 0.65; 95% CI, 0.53 to 0.79; P=1.06×10−5). CONCLUSIONS We identified a 3p21.31 gene cluster as a genetic susceptibility locus in patients with Covid-19 with respiratory failure and confirmed a potential involvement of the ABO blood-group system.
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U2 - 10.1056/NEJMoa2020283
DO - 10.1056/NEJMoa2020283
M3 - Article
C2 - 32558485
AN - SCOPUS:85087699779
SN - 0028-4793
VL - 383
SP - 1522
EP - 1534
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 16
ER -