{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:28:07Z","timestamp":1760149687023,"version":"build-2065373602"},"reference-count":60,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T00:00:00Z","timestamp":1693353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish National Research Council (CSIC)","award":["CSIC202020E086","AC19\/00106","RD21\/0006\/0006","PMP21\/00165","PI21\/01088","FI19\/00309","CD20\/00043"],"award-info":[{"award-number":["CSIC202020E086","AC19\/00106","RD21\/0006\/0006","PMP21\/00165","PI21\/01088","FI19\/00309","CD20\/00043"]}]},{"name":"European Commission\u2014NextGenerationEU","award":["CSIC202020E086","AC19\/00106","RD21\/0006\/0006","PMP21\/00165","PI21\/01088","FI19\/00309","CD20\/00043"],"award-info":[{"award-number":["CSIC202020E086","AC19\/00106","RD21\/0006\/0006","PMP21\/00165","PI21\/01088","FI19\/00309","CD20\/00043"]}]},{"name":"RICORS","award":["CSIC202020E086","AC19\/00106","RD21\/0006\/0006","PMP21\/00165","PI21\/01088","FI19\/00309","CD20\/00043"],"award-info":[{"award-number":["CSIC202020E086","AC19\/00106","RD21\/0006\/0006","PMP21\/00165","PI21\/01088","FI19\/00309","CD20\/00043"]}]},{"name":"FEDER, NextGeneration EU, the PREVICTUS project","award":["CSIC202020E086","AC19\/00106","RD21\/0006\/0006","PMP21\/00165","PI21\/01088","FI19\/00309","CD20\/00043"],"award-info":[{"award-number":["CSIC202020E086","AC19\/00106","RD21\/0006\/0006","PMP21\/00165","PI21\/01088","FI19\/00309","CD20\/00043"]}]},{"name":"COPYCTUS project","award":["CSIC202020E086","AC19\/00106","RD21\/0006\/0006","PMP21\/00165","PI21\/01088","FI19\/00309","CD20\/00043"],"award-info":[{"award-number":["CSIC202020E086","AC19\/00106","RD21\/0006\/0006","PMP21\/00165","PI21\/01088","FI19\/00309","CD20\/00043"]}]},{"name":"Catalan Government","award":["CSIC202020E086","AC19\/00106","RD21\/0006\/0006","PMP21\/00165","PI21\/01088","FI19\/00309","CD20\/00043"],"award-info":[{"award-number":["CSIC202020E086","AC19\/00106","RD21\/0006\/0006","PMP21\/00165","PI21\/01088","FI19\/00309","CD20\/00043"]}]},{"name":"ontratos Predoctorales de Formaci\u00f3n en Investigaci\u00f3n en Salud","award":["CSIC202020E086","AC19\/00106","RD21\/0006\/0006","PMP21\/00165","PI21\/01088","FI19\/00309","CD20\/00043"],"award-info":[{"award-number":["CSIC202020E086","AC19\/00106","RD21\/0006\/0006","PMP21\/00165","PI21\/01088","FI19\/00309","CD20\/00043"]}]},{"name":"The Belgian National Funds for Scientific Research and Fondation L\u00e9on Fredericq","award":["CSIC202020E086","AC19\/00106","RD21\/0006\/0006","PMP21\/00165","PI21\/01088","FI19\/00309","CD20\/00043"],"award-info":[{"award-number":["CSIC202020E086","AC19\/00106","RD21\/0006\/0006","PMP21\/00165","PI21\/01088","FI19\/00309","CD20\/00043"]}]},{"name":"Sara Borrel contract","award":["CSIC202020E086","AC19\/00106","RD21\/0006\/0006","PMP21\/00165","PI21\/01088","FI19\/00309","CD20\/00043"],"award-info":[{"award-number":["CSIC202020E086","AC19\/00106","RD21\/0006\/0006","PMP21\/00165","PI21\/01088","FI19\/00309","CD20\/00043"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 &lt; 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 \u00d7 10\u22122, se = 0.02), previously associated with CES, HS6ST1 (rs4662630, IS-COV beta = \u22120.04, p-value = 1.3 \u00d7 10\u22123, se = 0.01), TMEM132E (rs12941838 IS-COV beta = 0.05, p-value = 3.6 \u00d7 10\u22124, se = 0.01), and RFFL (rs797989 IS-COV beta = 0.03, p-value = 1.0 \u00d7 10\u22122, 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.<\/jats:p>","DOI":"10.3390\/ijms241713452","type":"journal-article","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T09:44:46Z","timestamp":1693388686000},"page":"13452","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Genetic Architecture of Ischaemic Strokes after COVID-19 Shows Similarities with Large Vessel Strokes"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7732-0665","authenticated-orcid":false,"given":"Laia","family":"Lluci\u00e0-Carol","sequence":"first","affiliation":[{"name":"Stroke Pharmacogenomics and Genetics, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau (IIB SANT PAU), Sant Quint\u00ed 77-79, 08041 Barcelona, Spain"},{"name":"Departament de Gen\u00e8tica i de Microbiologia, Universitat Aut\u00f2noma de Barcelona, 08193 Bellaterra, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Mui\u00f1o","sequence":"additional","affiliation":[{"name":"Stroke Pharmacogenomics and Genetics, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau (IIB SANT PAU), Sant Quint\u00ed 77-79, 08041 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Cullell","sequence":"additional","affiliation":[{"name":"Stroke Pharmacogenomics and Genetics, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau (IIB SANT PAU), Sant Quint\u00ed 77-79, 08041 Barcelona, Spain"},{"name":"Department of Neurology, Hospital Universitari M\u00fatuaTerrassa, Fundaci\u00f3 Doc\u00e8ncia i Recerca M\u00fatuaTerrassa, 08221 Terrassa, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6949-0699","authenticated-orcid":false,"given":"Jara","family":"C\u00e1rcel-M\u00e1rquez","sequence":"additional","affiliation":[{"name":"Stroke Pharmacogenomics and Genetics, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau (IIB SANT PAU), Sant Quint\u00ed 77-79, 08041 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8832-789X","authenticated-orcid":false,"given":"Miquel","family":"Lled\u00f3s","sequence":"additional","affiliation":[{"name":"Stroke Pharmacogenomics and Genetics, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau (IIB SANT PAU), Sant Quint\u00ed 77-79, 08041 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3229-5512","authenticated-orcid":false,"given":"Cristina","family":"Gallego-Fabrega","sequence":"additional","affiliation":[{"name":"Stroke Pharmacogenomics and Genetics, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau (IIB SANT PAU), Sant Quint\u00ed 77-79, 08041 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0414-037X","authenticated-orcid":false,"given":"Jes\u00fas","family":"Martin-Campos","sequence":"additional","affiliation":[{"name":"Stroke Pharmacogenomics and Genetics, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau (IIB SANT PAU), Sant Quint\u00ed 77-79, 08041 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9229-8649","authenticated-orcid":false,"given":"Joan","family":"Mart\u00ed-F\u00e0bregas","sequence":"additional","affiliation":[{"name":"Department of Neurology, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau (IIB SANT PAU), Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1428-8212","authenticated-orcid":false,"given":"Ana","family":"Aguilera-Sim\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Neurology, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau (IIB SANT PAU), Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna M.","family":"Planas","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research of Barcelona (IIBB), Spanish National Research Council (CSIC), 08036 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7888-7372","authenticated-orcid":false,"given":"Marta L.","family":"DeDiego","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, Centro Nacional de Biotecnolog\u00eda (CNB-CSIC), Campus Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alicia","family":"de Felipe Mimbrera","sequence":"additional","affiliation":[{"name":"Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria, Hospital Universitario Ram\u00f3n Y Cajal, 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1329-0943","authenticated-orcid":false,"given":"Jaime","family":"Masjuan","sequence":"additional","affiliation":[{"name":"Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria, Hospital Universitario Ram\u00f3n Y Cajal, 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebasti\u00e1n","family":"Garc\u00eda-Madrona","sequence":"additional","affiliation":[{"name":"Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria, Hospital Universitario Ram\u00f3n Y Cajal, 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3625-0987","authenticated-orcid":false,"given":"Tom\u00e1s","family":"Segura","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital of Albacete, 02006 Albacete, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther","family":"Gonz\u00e1lez-Villar","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital of Albacete, 02006 Albacete, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gemma","family":"Serrano-Heras","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital of Albacete, 02006 Albacete, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Dom\u00ednguez Mayoral","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Roc\u00edo, CSIC, Universidad de Sevilla, 410113 Seville, Spain"},{"name":"Department of Neurology, Hospital Universitario Virgen Macarena, 41009 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paloma","family":"Men\u00e9ndez-Valladares","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Roc\u00edo, CSIC, Universidad de Sevilla, 410113 Seville, Spain"},{"name":"Department of Neurology, Hospital Universitario Virgen Macarena, 41009 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan","family":"Montaner","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Roc\u00edo, CSIC, Universidad de Sevilla, 410113 Seville, Spain"},{"name":"Department of Neurology, Hospital Universitario Virgen Macarena, 41009 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Migeotte","sequence":"additional","affiliation":[{"name":"Fonds de la Recherche Scientifique (FNRS), 1000 Brussels, Belgium"},{"name":"Centre de G\u00e9n\u00e9tique Humaine, Hopital Erasme, Universit\u00e9 Libre de Bruxelles, 1050 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Souad","family":"Rahmouni","sequence":"additional","affiliation":[{"name":"Fonds de la Recherche Scientifique (FNRS), 1000 Brussels, Belgium"},{"name":"Department of Biomedical and Preclinical Sciences, Faculty of Medicine, GIGA-Insitute, University of Liege, 4000 Li\u00e8ge, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8192-1351","authenticated-orcid":false,"given":"Gilles","family":"Darcis","sequence":"additional","affiliation":[{"name":"Fonds de la Recherche Scientifique (FNRS), 1000 Brussels, Belgium"},{"name":"CHU of Liege, 4000 Li\u00e8ge, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Bernardo","sequence":"additional","affiliation":[{"name":"Mucosal Immunology Lab, Unidad de Excelencia del Instituto de Biomedicina y Gen\u00e9tica Molecular (IBGM), Universidad de Valladolid-CSIC, 47005 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Rojo","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Hospital Cl\u00ednico Universitario de Valladolid, Gerencia Regional de Salud de Castilla y Le\u00f3n (SACYL), 47003 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3105-5672","authenticated-orcid":false,"given":"Eva C.","family":"Schulte","sequence":"additional","affiliation":[{"name":"Institute of Virology, Technical University Munich\/Helmholtz Zentrum M\u00fcnchen, 81377 Munich, Germany"},{"name":"Institute of Psychiatric Phenomics and Genomics, University Hospital, LMU Munich University, 80336 Munich, Germany"},{"name":"Department of Psychiatry, University Hospital, LMU Munich University, 80336 Munich, Germany"},{"name":"Institute of Human Genetics, University Hospital Bonn, Medical Faculty, University of Bonn, 53127 Bonn, Germany"},{"name":"Department of Psychiatry and Psychotherapy, University Hospital Bonn, Medical Faculty, University of Bonn, 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9421-1911","authenticated-orcid":false,"given":"Ulrike","family":"Protzer","sequence":"additional","affiliation":[{"name":"Institute of Virology, Technical University Munich\/Helmholtz Zentrum M\u00fcnchen, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9268-0546","authenticated-orcid":false,"given":"Lisa","family":"Fricke","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0253-9056","authenticated-orcid":false,"given":"Christof","family":"Winter","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Pathobiochemistry, School of Medicine, Technische Universit\u00e4t M\u00fcnchen (TUM), 81675 Munich, Germany"},{"name":"TranslaTUM, Center for Translational Cancer Research, Technische Universit\u00e4t M\u00fcnchen, 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mari E. K.","family":"Niemi","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland (FIMM), University of Helsinki, 00014 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mattia","family":"Cordioli","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland (FIMM), University of Helsinki, 00014 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1628-4488","authenticated-orcid":false,"given":"Pilar","family":"Delgado","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Universitari de la Vall d\u2019Hebr\u00f3n, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Israel","family":"Fern\u00e1ndez-Cadenas","sequence":"additional","affiliation":[{"name":"Stroke Pharmacogenomics and Genetics, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau (IIB SANT PAU), Sant Quint\u00ed 77-79, 08041 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.thromres.2020.04.041","article-title":"Confirmation of the High Cumulative Incidence of Thrombotic Complications in Critically Ill ICU Patients with COVID-19: An Updated Analysis","volume":"191","author":"Klok","year":"2020","journal-title":"Thromb. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1001\/jamaneurol.2020.1127","article-title":"Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China","volume":"77","author":"Mao","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1161\/STROKEAHA.120.030995","article-title":"Acute Cerebrovascular Events in Hospitalized COVID-19 Patients","volume":"51","author":"Rothstein","year":"2020","journal-title":"Stroke"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.thromres.2020.04.024","article-title":"Venous and Arterial Thromboembolic Complications in COVID-19 Patients Admitted to an Academic Hospital in Milan, Italy","volume":"191","author":"Lodigiani","year":"2020","journal-title":"Thromb. 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