Genetic Architecture of Ischaemic Strokes after COVID-19 Shows Similarities with Large Vessel Strokes.
Por:
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
Publicada:
30 ago 2023
Ahead of Print:
30 ago 2023
Resumen:
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.
Filiaciones:
Llucià-Carol L:
Stroke Pharmacogenomics and Genetics, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain
Muiño E:
Stroke Pharmacogenomics and Genetics, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
Cullell N:
Stroke Pharmacogenomics and Genetics, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
Department of Neurology, Hospital Universitari MútuaTerrassa, Fundació Docència i Recerca MútuaTerrassa, 08221 Terrassa, Spain
Cárcel-Márquez J:
Stroke Pharmacogenomics and Genetics, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
Lledós M:
Stroke Pharmacogenomics and Genetics, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
Gallego-Fabrega C:
Stroke Pharmacogenomics and Genetics, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
Martin-Campos J:
Stroke Pharmacogenomics and Genetics, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
Martí-Fàbregas J:
Department of Neurology, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
Aguilera-Simón A:
Department of Neurology, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
Planas AM:
Institute for Biomedical Research of Barcelona (IIBB), Spanish National Research Council (CSIC), 08036 Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
DeDiego ML:
Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, 28049 Madrid, Spain
de Felipe Mimbrera A:
Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario Ramón Y Cajal, 28034 Madrid, Spain
Masjuan J:
Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario Ramón Y Cajal, 28034 Madrid, Spain
García-Madrona S:
Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario Ramón Y Cajal, 28034 Madrid, Spain
Segura T:
Department of Neurology, University Hospital of Albacete, 02006 Albacete, Spain
González-Villar E:
Department of Neurology, University Hospital of Albacete, 02006 Albacete, Spain
Serrano-Heras G:
Department of Neurology, University Hospital of Albacete, 02006 Albacete, Spain
Domínguez Mayoral A:
Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, 410113 Seville, Spain
Department of Neurology, Hospital Universitario Virgen Macarena, 41009 Seville, Spain
Menéndez-Valladares P:
Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, 410113 Seville, Spain
Department of Neurology, Hospital Universitario Virgen Macarena, 41009 Seville, Spain
Montaner J:
Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, 410113 Seville, Spain
Department of Neurology, Hospital Universitario Virgen Macarena, 41009 Seville, Spain
Migeotte I:
Fonds de la Recherche Scientifique (FNRS), 1000 Brussels, Belgium
Centre de Génétique Humaine, Hopital Erasme, Université Libre de Bruxelles, 1050 Brussels, Belgium
Rahmouni S:
Fonds de la Recherche Scientifique (FNRS), 1000 Brussels, Belgium
Department of Biomedical and Preclinical Sciences, Faculty of Medicine, GIGA-Insitute, University of Liege, 4000 Liège, Belgium
Darcis G:
Fonds de la Recherche Scientifique (FNRS), 1000 Brussels, Belgium
CHU of Liege, 4000 Liège, Belgium
Bernardo D:
Mucosal Immunology Lab, Unidad de Excelencia del Instituto de Biomedicina y Genética Molecular (IBGM), Universidad de Valladolid-CSIC, 47005 Valladolid, Spain
Rojo S:
Department of Microbiology, Hospital Clínico Universitario de Valladolid, Gerencia Regional de Salud de Castilla y León (SACYL), 47003 Valladolid, Spain
Schulte EC:
Institute of Virology, Technical University Munich/Helmholtz Zentrum München, 81377 Munich, Germany
Institute of Psychiatric Phenomics and Genomics, University Hospital, LMU Munich University, 80336 Munich, Germany
Department of Psychiatry, University Hospital, LMU Munich University, 80336 Munich, Germany
Institute of Human Genetics, University Hospital Bonn, Medical Faculty, University of Bonn, 53127 Bonn, Germany
Department of Psychiatry and Psychotherapy, University Hospital Bonn, Medical Faculty, University of Bonn, 53127 Bonn, Germany
Protzer U:
Institute of Virology, Technical University Munich/Helmholtz Zentrum München, 81377 Munich, Germany
Fricke L:
Department of Internal Medicine II, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany
Winter C:
Institute of Clinical Chemistry and Pathobiochemistry, School of Medicine, Technische Universität München (TUM), 81675 Munich, Germany
TranslaTUM, Center for Translational Cancer Research, Technische Universität München, 81675 Munich, Germany
Niemi MEK:
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, 00014 Helsinki, Finland
Cordioli M:
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, 00014 Helsinki, Finland
Delgado P:
Department of Neurology, Hospital Universitari de la Vall d'Hebrón, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain
Fernández-Cadenas I:
Stroke Pharmacogenomics and Genetics, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
Green Published, gold, All Open Access, Gold, Green
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