International Journal of Molecular Sciences (Aug 2023)
Genetic Architecture of Ischaemic Strokes after COVID-19 Shows Similarities with Large Vessel Strokes
- Laia Llucià-Carol,
- Elena Muiño,
- Natalia Cullell,
- Jara Cárcel-Márquez,
- Miquel Lledós,
- Cristina Gallego-Fabrega,
- Jesús Martin-Campos,
- Joan Martí-Fàbregas,
- Ana Aguilera-Simón,
- Anna M. Planas,
- Marta L. DeDiego,
- Alicia de Felipe Mimbrera,
- Jaime Masjuan,
- Sebastián García-Madrona,
- Tomás Segura,
- Esther González-Villar,
- Gemma Serrano-Heras,
- Ana Domínguez Mayoral,
- Paloma Menéndez-Valladares,
- Joan Montaner,
- Isabelle Migeotte,
- Souad Rahmouni,
- Gilles Darcis,
- David Bernardo,
- Silvia Rojo,
- Eva C. Schulte,
- Ulrike Protzer,
- Lisa Fricke,
- Christof Winter,
- Mari E. K. Niemi,
- Mattia Cordioli,
- Pilar Delgado,
- Israel Fernández-Cadenas
Affiliations
- Laia Llucià-Carol
- Stroke Pharmacogenomics and Genetics, Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
- Elena Muiño
- Stroke Pharmacogenomics and Genetics, Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
- Natalia Cullell
- Stroke Pharmacogenomics and Genetics, Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
- Jara Cárcel-Márquez
- Stroke Pharmacogenomics and Genetics, Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
- Miquel Lledós
- Stroke Pharmacogenomics and Genetics, Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
- Cristina Gallego-Fabrega
- Stroke Pharmacogenomics and Genetics, Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
- Jesús Martin-Campos
- Stroke Pharmacogenomics and Genetics, Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
- Joan Martí-Fàbregas
- Department of Neurology, Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
- Ana Aguilera-Simón
- Department of Neurology, Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
- Anna M. Planas
- Institute for Biomedical Research of Barcelona (IIBB), Spanish National Research Council (CSIC), 08036 Barcelona, Spain
- Marta L. DeDiego
- Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, 28049 Madrid, Spain
- Alicia de Felipe Mimbrera
- Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario Ramón Y Cajal, 28034 Madrid, Spain
- Jaime Masjuan
- Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario Ramón Y Cajal, 28034 Madrid, Spain
- Sebastián García-Madrona
- Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario Ramón Y Cajal, 28034 Madrid, Spain
- Tomás Segura
- Department of Neurology, University Hospital of Albacete, 02006 Albacete, Spain
- Esther González-Villar
- Department of Neurology, University Hospital of Albacete, 02006 Albacete, Spain
- Gemma Serrano-Heras
- Department of Neurology, University Hospital of Albacete, 02006 Albacete, Spain
- Ana Domínguez Mayoral
- Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, 410113 Seville, Spain
- Paloma Menéndez-Valladares
- Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, 410113 Seville, Spain
- Joan Montaner
- Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, 410113 Seville, Spain
- Isabelle Migeotte
- Fonds de la Recherche Scientifique (FNRS), 1000 Brussels, Belgium
- Souad Rahmouni
- Fonds de la Recherche Scientifique (FNRS), 1000 Brussels, Belgium
- Gilles Darcis
- Fonds de la Recherche Scientifique (FNRS), 1000 Brussels, Belgium
- David Bernardo
- Mucosal Immunology Lab, Unidad de Excelencia del Instituto de Biomedicina y Genética Molecular (IBGM), Universidad de Valladolid-CSIC, 47005 Valladolid, Spain
- Silvia Rojo
- Department of Microbiology, Hospital Clínico Universitario de Valladolid, Gerencia Regional de Salud de Castilla y León (SACYL), 47003 Valladolid, Spain
- Eva C. Schulte
- Institute of Virology, Technical University Munich/Helmholtz Zentrum München, 81377 Munich, Germany
- Ulrike Protzer
- Institute of Virology, Technical University Munich/Helmholtz Zentrum München, 81377 Munich, Germany
- Lisa Fricke
- Department of Internal Medicine II, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany
- Christof Winter
- Institute of Clinical Chemistry and Pathobiochemistry, School of Medicine, Technische Universität München (TUM), 81675 Munich, Germany
- Mari E. K. Niemi
- Institute for Molecular Medicine Finland (FIMM), University of Helsinki, 00014 Helsinki, Finland
- Mattia Cordioli
- Institute for Molecular Medicine Finland (FIMM), University of Helsinki, 00014 Helsinki, Finland
- Pilar Delgado
- Department of Neurology, Hospital Universitari de la Vall d’Hebrón, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain
- Israel Fernández-Cadenas
- Stroke Pharmacogenomics and Genetics, Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
- DOI
- https://doi.org/10.3390/ijms241713452
- Journal volume & issue
-
Vol. 24,
no. 17
p. 13452
Abstract
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 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.
Keywords