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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, A.M.* ; DeDiego, M.L.* ; de Felipe Mimbrera, A.* ; Masjuan, J.* ; Garcia-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, E.C. ; Protzer, U. ; Fricke, L.* ; Winter, C.* ; Niemi, M.E.K.* ; Cordioli, M.* ; Delgado, P.* ; Fernandez-Cadenas, I.*

Genetic architecture of ischaemic strokes after COVID-19 shows similarities with large vessel strokes.

Int. J. Mol. Sci. 24:14 (2023)
Publ. Version/Full Text DOI PMC
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Covid-19 ; Gwas ; Ischaemic Stroke ; Local Genetic Correlation ; Prs; Association; Complications; Tmem132e; Resource; Family; Loci
Language english
Publication Year 2023
HGF-reported in Year 2023
ISSN (print) / ISBN 1661-6596
e-ISSN 1422-0067
Journal International Journal of Molecular Sciences
Quellenangaben Volume: 24, Issue: 17, Pages: , Article Number: 14 Supplement: ,
Publisher MDPI
Publishing Place Basel
Reviewing status Peer reviewed
Institute(s) Institute of Virology (VIRO)
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Immune Response and Infection
PSP Element(s) G-502700-003
G-502799-701
Grants Belgian National Funds for Scientific Research and Fondation Leon Fredericq
Fondo Europeo de Desarrollo Regional (ISCIII-FEDER)
PFIS Contract from Instituto de Salud Carlos III (ISCIII)
Catalan Government (CERCA Program/Generalitat de Catalunya)
COPYCTUS project
PREVICTUS project
NextGeneration EU
FEDER
RICORS
Instituto de Salud Carlos III
European Commission-NextGenerationEU
Spanish National Research Council (CSIC)
DOI 10.3390/ijms241713452
WOS ID 001064155300001
Scopus ID 85170239813
PubMed ID 37686257
Erfassungsdatum 2023-10-18
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