Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes

Abstract

Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke subtypes. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.

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Affiliated Institutions

• Kyushu University JP
• Science for Life Laboratory SE
• Centre Hospitalier Universitaire de Lille FR
• University of Gothenburg SE
• University of Technology Sydney AU
• Harvard University US
• Children's National US
• Institute on Aging US
• University Hospital of Basel CH
• Johns Hopkins Medicine US
• University of Virginia US
• Yale University US
• King's College London GB
• Harbor–UCLA Medical Center US
• University of Alabama at Birmingham US
• Hope Center for Neurological Disorders US
• University of North Carolina at Chapel Hill US
• Leeds Teaching Hospitals NHS Trust GB
• Wake Forest University US
• Ludwig-Maximilians-Universität München DE
• Karolinska Institutet SE
• University of Edinburgh GB
• Massachusetts General Hospital US
• Leeds General Infirmary GB
• Hunter Medical Research Institute AU
• deCODE Genetics (Iceland) IS
• University of Mississippi Medical Center US
• Utrecht University NL
• Fred Hutch Cancer Center US
• The Lundquist Institute US
• Finnish Institute for Health and Welfare FI
• East Carolina University US
• University of Florida US
• University of Colorado Denver US
• Uppsala University SE
• University Medical Center Utrecht NL
• University of Cincinnati Medical Center US
• Fondazione IRCCS Istituto Neurologico Carlo Besta IT
• WinnMed US
• University of Colorado Anschutz Medical Campus US
• Brigham and Women's Hospital US
• KU Leuven BE
• Université de Lille FR
• LMU Klinikum DE
• Mayo Clinic US
• University of Cambridge GB
• Leiden University Medical Center NL
• Mayo Clinic in Florida US
• National Institute on Aging US
• St Peter's Hospital GB
• Emory University US
• Indian Institute of Science Bangalore IN
• Brown Foundation US
• University of British Columbia CA
• Lund University SE
• Boston University US
• University of Oxford GB
• Erasmus MC NL
• National Institutes of Health US
• University of Miami US
• Icelandic Heart Association IS
• Bordeaux Population Health FR
• University of Lincoln GB
• University of Maryland, Baltimore US
• RIKEN Center for Integrative Medical Sciences JP
• Inserm FR
• Stanford University US
• Population Health Research Institute CA
• Vall d'Hebron Institut de Recerca ES
• Florida College US
• Universitat Autònoma de Barcelona ES
• Institut Pasteur de Lille FR
• Université de Bordeaux FR
• MRC Epidemiology Unit GB
• Royal Holloway University of London GB
• McMaster University CA
• University of Washington US
• Johns Hopkins University US
• The University of Osaka JP
• Washington University in St. Louis US

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