Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes

Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found...

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Detalles Bibliográficos
Autor: Rabionet Janssen, Raquel
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2019
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/137453
Acceso en línea:https://hdl.handle.net/2445/137453
Access Level:acceso abierto
Palabra clave:Gens
Genòmica
Cromosomes
Genes
Genomics
Chromosomes
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spelling Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypesRabionet Janssen, RaquelGensGenòmicaCromosomesGenesGenomicsChromosomesStroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkagedisequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke subtypes. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.Nature Publishing Group2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/137453Articles publicats en revistes (Genètica, Microbiologia i Estadística)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1038/s41588-018-0058-3Nature Genetics, 2019, vol. 50, p. 524-537https://doi.org/10.1038/s41588-018-0058-3info:eu-repo/grantAgreement/EC/H2020/667375info:eu-repo/grantAgreement/EC/H2020/640643info:eu-repo/grantAgreement/EC/H2020/666881(c) Rabionet Janssen, Raquel, 2019info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1374532026-05-27T06:46:51Z
dc.title.none.fl_str_mv Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes
title Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes
spellingShingle Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes
Rabionet Janssen, Raquel
Gens
Genòmica
Cromosomes
Genes
Genomics
Chromosomes
title_short Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes
title_full Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes
title_fullStr Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes
title_full_unstemmed Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes
title_sort Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes
dc.creator.none.fl_str_mv Rabionet Janssen, Raquel
author Rabionet Janssen, Raquel
author_facet Rabionet Janssen, Raquel
author_role author
dc.subject.none.fl_str_mv Gens
Genòmica
Cromosomes
Genes
Genomics
Chromosomes
topic Gens
Genòmica
Cromosomes
Genes
Genomics
Chromosomes
description Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkagedisequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke subtypes. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/137453
url https://hdl.handle.net/2445/137453
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1038/s41588-018-0058-3
Nature Genetics, 2019, vol. 50, p. 524-537
https://doi.org/10.1038/s41588-018-0058-3
info:eu-repo/grantAgreement/EC/H2020/667375
info:eu-repo/grantAgreement/EC/H2020/640643
info:eu-repo/grantAgreement/EC/H2020/666881
dc.rights.none.fl_str_mv (c) Rabionet Janssen, Raquel, 2019
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Rabionet Janssen, Raquel, 2019
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv Articles publicats en revistes (Genètica, Microbiologia i Estadística)
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
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