A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death

The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associa...

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Autores: Minnai, Francesca, Biscarini, Filippo, Esposito, Martina, Dragani, Tommaso A., Bujanda, Luis, Rahmouni, Souad, Romero Gómez, Manuel, Colombo, Francesca
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/182532
Acceso en línea:https://hdl.handle.net/11441/182532
https://doi.org/10.1038/s41598-024-53310-x
Access Level:acceso abierto
Palabra clave:COVID-19
Genome-Wide Association Study
Genetic
SARS-CoV-2
Genotype
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spelling A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of deathMinnai, FrancescaBiscarini, FilippoEsposito, MartinaDragani, Tommaso A.Bujanda, LuisRahmouni, SouadRomero Gómez, ManuelColombo, FrancescaCOVID-19Genome-Wide Association StudyGeneticSARS-CoV-2GenotypeThe clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value < 5.0 × 10-8) association of the rs117011822 variant, on chromosome 11, of rs7208524 on chromosome 17, approaching the genome-wide threshold (P-value = 5.19 × 10-8). A total of 113 variants were associated with survival at P-value < 1.0 × 10-5 and most of them regulated the expression of genes involved in immune response (e.g., CD300 and KLR genes), or in lung repair and function (e.g., FGF19 and CDH13). Overall, our results suggest that germline variants may modulate COVID-19 risk of death, possibly through the regulation of gene expression in immune response and lung function pathways.Nature publishing group; nature portfolio; Springer Science and Business Media LLCMedicinaIstituto Buddista Italiano Soka Gakkai2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/182532https://doi.org/10.1038/s41598-024-53310-xreponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésScientific reports, 14 (1), 3000.2020-226 2016_RIC_3https://www.nature.com/articles/s41598-024-53310-xinfo:eu-repo/semantics/openAccessoai:idus.us.es:11441/1825322026-06-17T12:51:07Z
dc.title.none.fl_str_mv A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death
title A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death
spellingShingle A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death
Minnai, Francesca
COVID-19
Genome-Wide Association Study
Genetic
SARS-CoV-2
Genotype
title_short A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death
title_full A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death
title_fullStr A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death
title_full_unstemmed A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death
title_sort A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death
dc.creator.none.fl_str_mv Minnai, Francesca
Biscarini, Filippo
Esposito, Martina
Dragani, Tommaso A.
Bujanda, Luis
Rahmouni, Souad
Romero Gómez, Manuel
Colombo, Francesca
author Minnai, Francesca
author_facet Minnai, Francesca
Biscarini, Filippo
Esposito, Martina
Dragani, Tommaso A.
Bujanda, Luis
Rahmouni, Souad
Romero Gómez, Manuel
Colombo, Francesca
author_role author
author2 Biscarini, Filippo
Esposito, Martina
Dragani, Tommaso A.
Bujanda, Luis
Rahmouni, Souad
Romero Gómez, Manuel
Colombo, Francesca
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Medicina
Istituto Buddista Italiano Soka Gakkai
dc.subject.none.fl_str_mv COVID-19
Genome-Wide Association Study
Genetic
SARS-CoV-2
Genotype
topic COVID-19
Genome-Wide Association Study
Genetic
SARS-CoV-2
Genotype
description The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value < 5.0 × 10-8) association of the rs117011822 variant, on chromosome 11, of rs7208524 on chromosome 17, approaching the genome-wide threshold (P-value = 5.19 × 10-8). A total of 113 variants were associated with survival at P-value < 1.0 × 10-5 and most of them regulated the expression of genes involved in immune response (e.g., CD300 and KLR genes), or in lung repair and function (e.g., FGF19 and CDH13). Overall, our results suggest that germline variants may modulate COVID-19 risk of death, possibly through the regulation of gene expression in immune response and lung function pathways.
publishDate 2024
dc.date.none.fl_str_mv 2024
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/11441/182532
https://doi.org/10.1038/s41598-024-53310-x
url https://hdl.handle.net/11441/182532
https://doi.org/10.1038/s41598-024-53310-x
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Scientific reports, 14 (1), 3000.
2020-226 2016_RIC_3
https://www.nature.com/articles/s41598-024-53310-x
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature publishing group; nature portfolio; Springer Science and Business Media LLC
publisher.none.fl_str_mv Nature publishing group; nature portfolio; Springer Science and Business Media LLC
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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