Leveraging Genetic Data to Elucidate the Relationship Between COVID-19 and Ischemic Stroke

Background The relationship between COVID-19 and ischemic stroke is poorly understood due to potential unmeasured confounding and reverse causation. We aimed to leverage genetic data to triangulate reported associations. Methods and Results Analyses primarily focused on critical COVID-19, defined as...

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Autores: Zuber, V, Cameron, A, Myserlis, EP, Bottolo, L, Fernandez-Cadenas, I, Burgess, S, Anderson, CD, Dawson, J, Gill, D
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p5203
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=5203
Access Level:acceso abierto
Palabra clave:COVID-19
cross-trait linkage disequilibrium score regression
ischemic stroke
Mendelian randomization
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spelling Leveraging Genetic Data to Elucidate the Relationship Between COVID-19 and Ischemic StrokeZuber, VCameron, AMyserlis, EPBottolo, LFernandez-Cadenas, IBurgess, SAnderson, CDDawson, JGill, DCOVID-19cross-trait linkage disequilibrium score regressionischemic strokeMendelian randomizationBackground The relationship between COVID-19 and ischemic stroke is poorly understood due to potential unmeasured confounding and reverse causation. We aimed to leverage genetic data to triangulate reported associations. Methods and Results Analyses primarily focused on critical COVID-19, defined as hospitalization with COVID-19 requiring respiratory support or resulting in death. Cross-trait linkage disequilibrium score regression was used to estimate genetic correlations of critical COVID-19 with ischemic stroke, other related cardiovascular outcomes, and risk factors common to both COVID-19 and cardiovascular disease (body mass index, smoking and chronic inflammation, estimated using C-reactive protein). Mendelian randomization analysis was performed to investigate whether liability to critical COVID-19 was associated with increased risk of any cardiovascular outcome for which genetic correlation was identified. There was evidence of genetic correlation between critical COVID-19 and ischemic stroke (r(g)=0.29, false discovery rate [FDR]=0.012), body mass index (r(g)=0.21, FDR=0.00002), and C-reactive protein (r(g)=0.20, FDR=0.00035), but no other trait investigated. In Mendelian randomization, liability to critical COVID-19 was associated with increased risk of ischemic stroke (odds ratio [OR] per logOR increase in genetically predicted critical COVID-19 liability 1.03, 95% CI 1.00-1.06, P-value=0.03). Similar estimates were obtained for ischemic stroke subtypes. Consistent estimates were also obtained when performing statistical sensitivity analyses more robust to the inclusion of pleiotropic variants, including multivariable Mendelian randomization analyses adjusting for potential genetic confounding through body mass index, smoking, and chronic inflammation. There was no evidence to suggest that genetic liability to ischemic stroke increased the risk of critical COVID-19. Conclusions These data support that liability to critical COVID-19 is associated with an increased risk of ischemic stroke. The host response predisposing to severe COVID-19 is likely to increase the risk of ischemic stroke, independent of other potentially mitigating risk factors.WILEY2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=5203Journal of the American Heart AssociationISSN: 20479980reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p52032026-06-14T12:41:47Z
dc.title.none.fl_str_mv Leveraging Genetic Data to Elucidate the Relationship Between COVID-19 and Ischemic Stroke
title Leveraging Genetic Data to Elucidate the Relationship Between COVID-19 and Ischemic Stroke
spellingShingle Leveraging Genetic Data to Elucidate the Relationship Between COVID-19 and Ischemic Stroke
Zuber, V
COVID-19
cross-trait linkage disequilibrium score regression
ischemic stroke
Mendelian randomization
title_short Leveraging Genetic Data to Elucidate the Relationship Between COVID-19 and Ischemic Stroke
title_full Leveraging Genetic Data to Elucidate the Relationship Between COVID-19 and Ischemic Stroke
title_fullStr Leveraging Genetic Data to Elucidate the Relationship Between COVID-19 and Ischemic Stroke
title_full_unstemmed Leveraging Genetic Data to Elucidate the Relationship Between COVID-19 and Ischemic Stroke
title_sort Leveraging Genetic Data to Elucidate the Relationship Between COVID-19 and Ischemic Stroke
dc.creator.none.fl_str_mv Zuber, V
Cameron, A
Myserlis, EP
Bottolo, L
Fernandez-Cadenas, I
Burgess, S
Anderson, CD
Dawson, J
Gill, D
author Zuber, V
author_facet Zuber, V
Cameron, A
Myserlis, EP
Bottolo, L
Fernandez-Cadenas, I
Burgess, S
Anderson, CD
Dawson, J
Gill, D
author_role author
author2 Cameron, A
Myserlis, EP
Bottolo, L
Fernandez-Cadenas, I
Burgess, S
Anderson, CD
Dawson, J
Gill, D
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv COVID-19
cross-trait linkage disequilibrium score regression
ischemic stroke
Mendelian randomization
topic COVID-19
cross-trait linkage disequilibrium score regression
ischemic stroke
Mendelian randomization
description Background The relationship between COVID-19 and ischemic stroke is poorly understood due to potential unmeasured confounding and reverse causation. We aimed to leverage genetic data to triangulate reported associations. Methods and Results Analyses primarily focused on critical COVID-19, defined as hospitalization with COVID-19 requiring respiratory support or resulting in death. Cross-trait linkage disequilibrium score regression was used to estimate genetic correlations of critical COVID-19 with ischemic stroke, other related cardiovascular outcomes, and risk factors common to both COVID-19 and cardiovascular disease (body mass index, smoking and chronic inflammation, estimated using C-reactive protein). Mendelian randomization analysis was performed to investigate whether liability to critical COVID-19 was associated with increased risk of any cardiovascular outcome for which genetic correlation was identified. There was evidence of genetic correlation between critical COVID-19 and ischemic stroke (r(g)=0.29, false discovery rate [FDR]=0.012), body mass index (r(g)=0.21, FDR=0.00002), and C-reactive protein (r(g)=0.20, FDR=0.00035), but no other trait investigated. In Mendelian randomization, liability to critical COVID-19 was associated with increased risk of ischemic stroke (odds ratio [OR] per logOR increase in genetically predicted critical COVID-19 liability 1.03, 95% CI 1.00-1.06, P-value=0.03). Similar estimates were obtained for ischemic stroke subtypes. Consistent estimates were also obtained when performing statistical sensitivity analyses more robust to the inclusion of pleiotropic variants, including multivariable Mendelian randomization analyses adjusting for potential genetic confounding through body mass index, smoking, and chronic inflammation. There was no evidence to suggest that genetic liability to ischemic stroke increased the risk of critical COVID-19. Conclusions These data support that liability to critical COVID-19 is associated with an increased risk of ischemic stroke. The host response predisposing to severe COVID-19 is likely to increase the risk of ischemic stroke, independent of other potentially mitigating risk factors.
publishDate 2021
dc.date.none.fl_str_mv 2021
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://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=5203
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=5203
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv WILEY
publisher.none.fl_str_mv WILEY
dc.source.none.fl_str_mv Journal of the American Heart Association
ISSN: 20479980
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
repository.name.fl_str_mv
repository.mail.fl_str_mv
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