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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Verena Zuber, Alan Cameron, Evangelos P. Myserlis, Leonardo Bottolo, Israel Fernandez‐Cadenas, Stephen Burgess, Christopher D. Anderson, Jesse Dawson, Dipender Gill
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	COVID‐19 cross‐trait linkage disequilibrium score regression ischemic stroke Mendelian randomization Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/efd6862a711f49dab73f5f4d00680cd5
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:efd6862a711f49dab73f5f4d00680cd5
record_format	dspace
spelling	oai:doaj.org-article:efd6862a711f49dab73f5f4d00680cd52021-11-16T10:22:43ZLeveraging Genetic Data to Elucidate the Relationship Between COVID‐19 and Ischemic Stroke10.1161/JAHA.121.0224332047-9980https://doaj.org/article/efd6862a711f49dab73f5f4d00680cd52021-11-01T00:00:00Zhttps://www.ahajournals.org/doi/10.1161/JAHA.121.022433https://doaj.org/toc/2047-9980Background 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 (rg=0.29, false discovery rate [FDR]=0.012), body mass index (rg=0.21, FDR=0.00002), and C‐reactive protein (rg=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.Verena ZuberAlan CameronEvangelos P. MyserlisLeonardo BottoloIsrael Fernandez‐CadenasStephen BurgessChristopher D. AndersonJesse DawsonDipender GillWileyarticleCOVID‐19cross‐trait linkage disequilibrium score regressionischemic strokeMendelian randomizationDiseases of the circulatory (Cardiovascular) systemRC666-701ENJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 10, Iss 22 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	COVID‐19 cross‐trait linkage disequilibrium score regression ischemic stroke Mendelian randomization Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	COVID‐19 cross‐trait linkage disequilibrium score regression ischemic stroke Mendelian randomization Diseases of the circulatory (Cardiovascular) system RC666-701 Verena Zuber Alan Cameron Evangelos P. Myserlis Leonardo Bottolo Israel Fernandez‐Cadenas Stephen Burgess Christopher D. Anderson Jesse Dawson Dipender Gill Leveraging Genetic Data to Elucidate the Relationship Between COVID‐19 and Ischemic Stroke
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 (rg=0.29, false discovery rate [FDR]=0.012), body mass index (rg=0.21, FDR=0.00002), and C‐reactive protein (rg=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.
format	article
author	Verena Zuber Alan Cameron Evangelos P. Myserlis Leonardo Bottolo Israel Fernandez‐Cadenas Stephen Burgess Christopher D. Anderson Jesse Dawson Dipender Gill
author_facet	Verena Zuber Alan Cameron Evangelos P. Myserlis Leonardo Bottolo Israel Fernandez‐Cadenas Stephen Burgess Christopher D. Anderson Jesse Dawson Dipender Gill
author_sort	Verena Zuber
title	Leveraging Genetic Data to Elucidate the Relationship Between COVID‐19 and Ischemic Stroke
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
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/efd6862a711f49dab73f5f4d00680cd5
work_keys_str_mv	AT verenazuber leveraginggeneticdatatoelucidatetherelationshipbetweencovid19andischemicstroke AT alancameron leveraginggeneticdatatoelucidatetherelationshipbetweencovid19andischemicstroke AT evangelospmyserlis leveraginggeneticdatatoelucidatetherelationshipbetweencovid19andischemicstroke AT leonardobottolo leveraginggeneticdatatoelucidatetherelationshipbetweencovid19andischemicstroke AT israelfernandezcadenas leveraginggeneticdatatoelucidatetherelationshipbetweencovid19andischemicstroke AT stephenburgess leveraginggeneticdatatoelucidatetherelationshipbetweencovid19andischemicstroke AT christopherdanderson leveraginggeneticdatatoelucidatetherelationshipbetweencovid19andischemicstroke AT jessedawson leveraginggeneticdatatoelucidatetherelationshipbetweencovid19andischemicstroke AT dipendergill leveraginggeneticdatatoelucidatetherelationshipbetweencovid19andischemicstroke
_version_	1718426580347256832

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

Ejemplares similares