Genomewide Association Study of Severe Covid-19 with Respiratory Failure

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...

ver descrição completa

Detalhes bibliográficos
Autores: Ellinghaus, David, Degenhardt, F., Bujanda, Luis, Moreno Aguado, Víctor, Severe Covid-19 GWAS Group
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2020
País:España
Recursos:Universidad de Barcelona
Repositório:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/173813
Acesso em linha:https://hdl.handle.net/2445/173813
Access Level:Acceso aberto
Palavra-chave:SARS-CoV-2
COVID-19
Genòmica
Genomics
id ES_e40d2bd1d9a3fb003642b8ef2b3ce132
oai_identifier_str oai:diposit.ub.edu:2445/173813
network_acronym_str ES
network_name_str España
repository_id_str
spelling Genomewide Association Study of Severe Covid-19 with Respiratory FailureEllinghaus, DavidDegenhardt, F.Bujanda, LuisMoreno Aguado, VíctorSevere Covid-19 GWAS GroupSARS-CoV-2COVID-19GenòmicaSARS-CoV-2COVID-19GenomicsBackground: 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. ResultsWe 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<5x10(-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=1.15x10(-10); and odds ratio, 1.32; 95% CI, 1.20 to 1.47; P=4.95x10(-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=1.48x10(-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=1.06x10(-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. (Funded by Stein Erik Hagen and others.) During the peak of hospitalizations of patients with severe Covid-19 in Italy and Spain in March, a group of researchers in these and other countries obtained and analyzed samples, resulting in the identification of two chromosomal loci associated with the disorder.Massachusetts Medical Society2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/173813Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1056/NEJMoa2020283New England Journal of Medicine, 2020, vol. 383, num. 16, p. 1522-1534https://doi.org/10.1056/NEJMoa2020283(c) Massachusetts Medical Society, 2020info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1738132026-05-27T06:46:51Z
dc.title.none.fl_str_mv Genomewide Association Study of Severe Covid-19 with Respiratory Failure
title Genomewide Association Study of Severe Covid-19 with Respiratory Failure
spellingShingle Genomewide Association Study of Severe Covid-19 with Respiratory Failure
Ellinghaus, David
SARS-CoV-2
COVID-19
Genòmica
SARS-CoV-2
COVID-19
Genomics
title_short Genomewide Association Study of Severe Covid-19 with Respiratory Failure
title_full Genomewide Association Study of Severe Covid-19 with Respiratory Failure
title_fullStr Genomewide Association Study of Severe Covid-19 with Respiratory Failure
title_full_unstemmed Genomewide Association Study of Severe Covid-19 with Respiratory Failure
title_sort Genomewide Association Study of Severe Covid-19 with Respiratory Failure
dc.creator.none.fl_str_mv Ellinghaus, David
Degenhardt, F.
Bujanda, Luis
Moreno Aguado, Víctor
Severe Covid-19 GWAS Group
author Ellinghaus, David
author_facet Ellinghaus, David
Degenhardt, F.
Bujanda, Luis
Moreno Aguado, Víctor
Severe Covid-19 GWAS Group
author_role author
author2 Degenhardt, F.
Bujanda, Luis
Moreno Aguado, Víctor
Severe Covid-19 GWAS Group
author2_role author
author
author
author
dc.subject.none.fl_str_mv SARS-CoV-2
COVID-19
Genòmica
SARS-CoV-2
COVID-19
Genomics
topic SARS-CoV-2
COVID-19
Genòmica
SARS-CoV-2
COVID-19
Genomics
description 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. ResultsWe 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<5x10(-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=1.15x10(-10); and odds ratio, 1.32; 95% CI, 1.20 to 1.47; P=4.95x10(-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=1.48x10(-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=1.06x10(-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. (Funded by Stein Erik Hagen and others.) During the peak of hospitalizations of patients with severe Covid-19 in Italy and Spain in March, a group of researchers in these and other countries obtained and analyzed samples, resulting in the identification of two chromosomal loci associated with the disorder.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/173813
url https://hdl.handle.net/2445/173813
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1056/NEJMoa2020283
New England Journal of Medicine, 2020, vol. 383, num. 16, p. 1522-1534
https://doi.org/10.1056/NEJMoa2020283
dc.rights.none.fl_str_mv (c) Massachusetts Medical Society, 2020
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Massachusetts Medical Society, 2020
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Massachusetts Medical Society
publisher.none.fl_str_mv Massachusetts Medical Society
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869422557359243264
score 15,301629

Registros relacionados