Genetic Architecture of Ischaemic Strokes after COVID-19 Shows Similarities with Large Vessel Strokes.

We aimed to analyse whether patients with ischaemic stroke (IS) occurring within eight days after the onset of COVID-19 (IS-COV) are associated with a specific aetiology of IS. We used SUPERGNOVA to identify genome regions that correlate between the IS-COV cohort (73 IS-COV cases vs. 701 population...

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Autores: Llucià-Carol L, Muiño E, Cullell N, Cárcel-Márquez J, Lledós M, Gallego-Fabrega C, Martin-Campos J, Martí-Fàbregas J, Aguilera-Simón A, Planas AM, DeDiego ML, de Felipe Mimbrera A, Masjuan J, García-Madrona S, Segura T, González-Villar E, Serrano-Heras G, Domínguez Mayoral A, Menéndez-Valladares P, Montaner J, Migeotte I, Rahmouni S, Darcis G, Bernardo D, Rojo S, Schulte EC, Protzer U, Fricke L, Winter C, Niemi MEK, Cordioli M, Delgado P, Fernández-Cadenas I
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
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:p17164
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17164
Access Level:acceso abierto
Palabra clave:COVID-19
GWAS
PRS
ischaemic stroke
local genetic correlation
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spelling Genetic Architecture of Ischaemic Strokes after COVID-19 Shows Similarities with Large Vessel Strokes.Llucià-Carol LMuiño ECullell NCárcel-Márquez JLledós MGallego-Fabrega CMartin-Campos JMartí-Fàbregas JAguilera-Simón APlanas AMDeDiego MLde Felipe Mimbrera AMasjuan JGarcía-Madrona SSegura TGonzález-Villar ESerrano-Heras GDomínguez Mayoral AMenéndez-Valladares PMontaner JMigeotte IRahmouni SDarcis GBernardo DRojo SSchulte ECProtzer UFricke LWinter CNiemi MEKCordioli MDelgado PFernández-Cadenas ICOVID-19GWASPRSischaemic strokelocal genetic correlationWe aimed to analyse whether patients with ischaemic stroke (IS) occurring within eight days after the onset of COVID-19 (IS-COV) are associated with a specific aetiology of IS. We used SUPERGNOVA to identify genome regions that correlate between the IS-COV cohort (73 IS-COV cases vs. 701 population controls) and different aetiological subtypes. Polygenic risk scores (PRSs) for each subtype were generated and tested in the IS-COV cohort using PRSice-2 and PLINK to find genetic associations. Both analyses used the IS-COV cohort and GWAS from MEGASTROKE (67,162 stroke patients vs. 454,450 population controls), GIGASTROKE (110,182 vs. 1,503,898), and the NINDS Stroke Genetics Network (16,851 vs. 32,473). Three genomic regions were associated (p-value < 0.05) with large artery atherosclerosis (LAA) and cardioembolic stroke (CES). We found four loci targeting the genes PITX2 (rs10033464, IS-COV beta = 0.04, p-value = 2.3 × 10(-2), se = 0.02), previously associated with CES, HS6ST1 (rs4662630, IS-COV beta = -0.04, p-value = 1.3 × 10(-3), se = 0.01), TMEM132E (rs12941838 IS-COV beta = 0.05, p-value = 3.6 × 10(-4), se = 0.01), and RFFL (rs797989 IS-COV beta = 0.03, p-value = 1.0 × 10(-2), se = 0.01). A statistically significant PRS was observed for LAA. Our results suggest that IS-COV cases are genetically similar to LAA and CES subtypes. Larger cohorts are needed to assess if the genetic factors in IS-COV cases are shared with the general population or specific to viral infection.MDPI2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17164INTERNATIONAL JOURNAL OF MOLECULAR SCIENCESISSN: 16616596ISSNe: 14220067reponame: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:p171642026-06-14T12:41:47Z
dc.title.none.fl_str_mv Genetic Architecture of Ischaemic Strokes after COVID-19 Shows Similarities with Large Vessel Strokes.
title Genetic Architecture of Ischaemic Strokes after COVID-19 Shows Similarities with Large Vessel Strokes.
spellingShingle Genetic Architecture of Ischaemic Strokes after COVID-19 Shows Similarities with Large Vessel Strokes.
Llucià-Carol L
COVID-19
GWAS
PRS
ischaemic stroke
local genetic correlation
title_short Genetic Architecture of Ischaemic Strokes after COVID-19 Shows Similarities with Large Vessel Strokes.
title_full Genetic Architecture of Ischaemic Strokes after COVID-19 Shows Similarities with Large Vessel Strokes.
title_fullStr Genetic Architecture of Ischaemic Strokes after COVID-19 Shows Similarities with Large Vessel Strokes.
title_full_unstemmed Genetic Architecture of Ischaemic Strokes after COVID-19 Shows Similarities with Large Vessel Strokes.
title_sort Genetic Architecture of Ischaemic Strokes after COVID-19 Shows Similarities with Large Vessel Strokes.
dc.creator.none.fl_str_mv Llucià-Carol L
Muiño E
Cullell N
Cárcel-Márquez J
Lledós M
Gallego-Fabrega C
Martin-Campos J
Martí-Fàbregas J
Aguilera-Simón A
Planas AM
DeDiego ML
de Felipe Mimbrera A
Masjuan J
García-Madrona S
Segura T
González-Villar E
Serrano-Heras G
Domínguez Mayoral A
Menéndez-Valladares P
Montaner J
Migeotte I
Rahmouni S
Darcis G
Bernardo D
Rojo S
Schulte EC
Protzer U
Fricke L
Winter C
Niemi MEK
Cordioli M
Delgado P
Fernández-Cadenas I
author Llucià-Carol L
author_facet Llucià-Carol L
Muiño E
Cullell N
Cárcel-Márquez J
Lledós M
Gallego-Fabrega C
Martin-Campos J
Martí-Fàbregas J
Aguilera-Simón A
Planas AM
DeDiego ML
de Felipe Mimbrera A
Masjuan J
García-Madrona S
Segura T
González-Villar E
Serrano-Heras G
Domínguez Mayoral A
Menéndez-Valladares P
Montaner J
Migeotte I
Rahmouni S
Darcis G
Bernardo D
Rojo S
Schulte EC
Protzer U
Fricke L
Winter C
Niemi MEK
Cordioli M
Delgado P
Fernández-Cadenas I
author_role author
author2 Muiño E
Cullell N
Cárcel-Márquez J
Lledós M
Gallego-Fabrega C
Martin-Campos J
Martí-Fàbregas J
Aguilera-Simón A
Planas AM
DeDiego ML
de Felipe Mimbrera A
Masjuan J
García-Madrona S
Segura T
González-Villar E
Serrano-Heras G
Domínguez Mayoral A
Menéndez-Valladares P
Montaner J
Migeotte I
Rahmouni S
Darcis G
Bernardo D
Rojo S
Schulte EC
Protzer U
Fricke L
Winter C
Niemi MEK
Cordioli M
Delgado P
Fernández-Cadenas I
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv COVID-19
GWAS
PRS
ischaemic stroke
local genetic correlation
topic COVID-19
GWAS
PRS
ischaemic stroke
local genetic correlation
description We aimed to analyse whether patients with ischaemic stroke (IS) occurring within eight days after the onset of COVID-19 (IS-COV) are associated with a specific aetiology of IS. We used SUPERGNOVA to identify genome regions that correlate between the IS-COV cohort (73 IS-COV cases vs. 701 population controls) and different aetiological subtypes. Polygenic risk scores (PRSs) for each subtype were generated and tested in the IS-COV cohort using PRSice-2 and PLINK to find genetic associations. Both analyses used the IS-COV cohort and GWAS from MEGASTROKE (67,162 stroke patients vs. 454,450 population controls), GIGASTROKE (110,182 vs. 1,503,898), and the NINDS Stroke Genetics Network (16,851 vs. 32,473). Three genomic regions were associated (p-value < 0.05) with large artery atherosclerosis (LAA) and cardioembolic stroke (CES). We found four loci targeting the genes PITX2 (rs10033464, IS-COV beta = 0.04, p-value = 2.3 × 10(-2), se = 0.02), previously associated with CES, HS6ST1 (rs4662630, IS-COV beta = -0.04, p-value = 1.3 × 10(-3), se = 0.01), TMEM132E (rs12941838 IS-COV beta = 0.05, p-value = 3.6 × 10(-4), se = 0.01), and RFFL (rs797989 IS-COV beta = 0.03, p-value = 1.0 × 10(-2), se = 0.01). A statistically significant PRS was observed for LAA. Our results suggest that IS-COV cases are genetically similar to LAA and CES subtypes. Larger cohorts are needed to assess if the genetic factors in IS-COV cases are shared with the general population or specific to viral infection.
publishDate 2023
dc.date.none.fl_str_mv 2023
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=17164
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17164
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 MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN: 16616596
ISSNe: 14220067
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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score 15.81155

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