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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)

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Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.

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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

Corresponding Author

Keywords Covid-19 ; Gwas ; Ischaemic Stroke ; Local Genetic Correlation ; Prs; Association; Complications; Tmem132e; Resource; Family; Loci

ISSN (print) / ISBN 1422-0067

e-ISSN 1661-6596

Journal International Journal of Molecular Sciences

Quellenangaben Volume: 24, Issue: 17, Article Number: 14

Publisher MDPI

Publishing Place Basel

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Virology (VIRO)

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)