Stroke genetics informs drug discovery and risk prediction across ancestries

Affiliations

• ¹ Bordeaux Population Health Research Center, University of Bordeaux, Inserm, UMR 1219, Bordeaux, France.
• ² Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.
• ³ Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan.
• ⁴ Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
• ⁵ Institute of Mathematics and Statistics, University of Tartu, Tartu, Estonia.
• ⁶ Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
• ⁷ Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA, USA.
• ⁸ TIMI Study Group, Boston, MA, USA.
• ⁹ Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
• ¹⁰ Division of Molecular Pathology, Institute of Medical Sciences, The University of Tokyo, Tokyo, Japan.
• ¹¹ Laboratory of Complex Trait Genomics, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
• ¹² Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
• ¹³ Program in Medical and Population Genetics, Broad Institute of Harvard and the Massachusetts Institute of Technology, Cambridge, MA, USA.
• ¹⁴ Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
• ¹⁵ Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, Taiwan.
• ¹⁶ Department of Internal Medicine, University of Turku, Turku, Finland.
• ¹⁷ Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Turku, Finland.
• ¹⁸ Nuffield Department of Population Health, University of Oxford, Oxford, UK.
• ¹⁹ Department of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway.
• ²⁰ K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
• ²¹ Department of Neurology, Oslo University Hospital, Oslo, Norway.
• ²² Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
• ²³ Department of Neurology and Cerebrovascular Disease Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
• ²⁴ Rajendra Institute of Medical Sciences, Ranchi, India.
• ²⁵ Thrombosis and Atherosclerosis Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada.
• ²⁶ Department of Pathology and Molecular Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
• ²⁷ Department of Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
• ²⁸ Center for Genomic and Precision Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria.
• ²⁹ Neuroscience and Ageing Research Unit Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria.
• ³⁰ Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
• ³¹ Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
• ³² The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
• ³³ Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
• ³⁴ Department of Clinical Biochemistry, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
• ³⁵ Department of Molecular and Functional Genomics, Weis Center for Research, Geisinger Health System, Danville, VA, USA.
• ³⁶ Department of Public Health Sciences, College of Medicine, The Pennsylvania State University, State College, PA, USA.
• ³⁷ Stroke Pharmacogenomics and Genetics Laboratory, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
• ³⁸ Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
• ³⁹ The Danish Twin Registry, Department of Public Health, University of Southern Denmark, Odense, Denmark.
• ⁴⁰ Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
• ⁴¹ Center for Alzheimer's and Related Dementias, National Institutes of Health, Bethesda, MD, USA.
• ⁴² Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
• ⁴³ Data Tecnica International, Glen Echo, MD, USA.
• ⁴⁴ Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
• ⁴⁵ Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA.
• ⁴⁶ British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
• ⁴⁷ Department of Genetics, Novo Nordisk Research Centre Oxford, Oxford, UK.
• ⁴⁸ Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA.
• ⁴⁹ Department of Surgery, University of Pennsylvania, Philadelphia, PA, USA.
• ⁵⁰ Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
• ⁵¹ University of Lille, INSERM U1167, RID-AGE, LabEx DISTALZ, Risk Factors and Molecular Determinants of Aging-Related Diseases, Lille, France.
• ⁵² CHU Lille, Public Health Department, Lille, France.
• ⁵³ Institut Pasteur de Lille, Lille, France.
• ⁵⁴ Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
• ⁵⁵ UMC Utrecht Brain Center, Department of Neurology and Neurosurgery, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands.
• ⁵⁶ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
• ⁵⁷ Department of Biostatistics, University of Washington, Seattle, WA, USA.
• ⁵⁸ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
• ⁵⁹ Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
• ⁶⁰ Research and Communication Unit for Musculoskeletal Health (FORMI), Department of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway.
• ⁶¹ Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
• ⁶² Harvard Medical School, Boston, MA, USA.
• ⁶³ MRC Population Health Research Unit, University of Oxford, Oxford, UK.
• ⁶⁴ Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA.
• ⁶⁵ NeuroGenomics and Informatics Center, Washington University School of Medicine, Saint Louis, MO, USA.
• ⁶⁶ VA Maryland Health Care System, Baltimore, MD, USA.
• ⁶⁷ Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA.
• ⁶⁸ Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, NY, USA.
• ⁶⁹ GenomesForLife-GCAT Lab Group, Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain.
• ⁷⁰ Klinik und Hochschulambulanz für Neurologie, Charité-Universitätsmedizin Berlin, Berlin, Germany.
• ⁷¹ Center for Stroke Research Berlin, Berlin, Germany.
• ⁷² German Center for Neurodegenerative Diseases (DZNE), partner site Berlin, Berlin, Germany.
• ⁷³ German Centre for Cardiovascular Research (DZHK), partner site Berlin, Berlin, Germany.
• ⁷⁴ Post-Graduation Program on Health and Environment, Department of Medicine and Joinville Stroke Biobank, University of the Region of Joinville, Santa Catarina, Brazil.
• ⁷⁵ Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
• ⁷⁶ Icelandic Heart Association, Kopavogur, Iceland.
• ⁷⁷ Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
• ⁷⁸ Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
• ⁷⁹ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
• ⁸⁰ Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland.
• ⁸¹ Institute for Molecular Medicine Finland, FIMM-HiLIFE, Helsinki, Finland.
• ⁸² Clinical Trial Service and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
• ⁸³ Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
• ⁸⁴ Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
• ⁸⁵ Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
• ⁸⁶ Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK.
• ⁸⁷ British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK.
• ⁸⁸ Department of Neurology, Donders Center for Medical Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.
• ⁸⁹ Los Angeles County Department of Public Health, Los Angeles, CA, USA.
• ⁹⁰ Institute of Biomedicine, Department of Laboratory Medicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
• ⁹¹ Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden.
• ⁹² Department of Health Care Administration and Management, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
• ⁹³ Department of Biology, Brody School of Medicine Center for Health Disparities, East Carolina University, Greenville, NC, USA.
• ⁹⁴ Department of Neurology and Geriatric Research and Education Clinical Center, VA Maryland Health Care System, Baltimore, MD, USA.
• ⁹⁵ Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
• ⁹⁶ Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD, USA.
• ⁹⁷ Department of Neurology, Korea University Guro Hospital, Seoul, Republic of Korea.
• ⁹⁸ Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
• ⁹⁹ Swiss Institute of Bioinformatics, Lausanne, Switzerland.
• ¹⁰⁰ University Center for Primary Care and Public Health, Lausanne, Switzerland.
• ¹⁰¹ Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.
• ¹⁰² Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
• ¹⁰³ Institute of Human Genetics, Technical University of Munich, Munich, Germany.
• ¹⁰⁴ Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
• ¹⁰⁵ Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
• ¹⁰⁶ Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, MD, USA.
• ¹⁰⁷ Institute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany.
• ¹⁰⁸ Department of Neurology, University Hospital Würzburg, Würzburg, Germany.
• ¹⁰⁹ The MIND Center, University of Mississippi Medical Center, Jackson, MS, USA.
• ¹¹⁰ Department of Clinical Biochemistry, Copenhagen University Hospital-Herlev and Gentofte, Copenhagen, Denmark.
• ¹¹¹ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
• ¹¹² College of Medicine Nursing and Health Science, NUI Galway, Galway, Ireland.
• ¹¹³ Department of Genome Informatics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
• ¹¹⁴ Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
• ¹¹⁵ Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan.
• ¹¹⁶ Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Japan.
• ¹¹⁷ Center for Infectious Disease Education and Research (CiDER), Osaka University, Suita, Japan.
• ¹¹⁸ Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
• ¹¹⁹ Institute of Epidemiology, Helmholtz Zentrum München,, German Research Center for Environmental Health, Neuherberg, Germany.
• ¹²⁰ Institute for Medical Information Processing, Biometry and Epidemiology, Ludwig Maximilian University Munich, Munich, Germany.
• ¹²¹ German Centre for Cardiovascular Research (DZHK), partner site Munich, Munich, Germany.
• ¹²² Department of Epidemiology, University of Washington, Seattle, WA, USA.
• ¹²³ Department of Health Systems and Population Health, University of Washington, Seattle, WA, USA.
• ¹²⁴ McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA, USA.
• ¹²⁵ Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA.
• ¹²⁶ Evelyn F. McKnight Brain Institute, Gainesville, FL, USA.
• ¹²⁷ Division of Cardiology, Department of Medicine, Columbia University, New York, NY, USA.
• ¹²⁸ Stroke Unit, Department of Neurology, Oslo University Hospital, Oslo, Norway.
• ¹²⁹ Research and Development, The Norwegian Air Ambulance Foundation, Oslo, Norway.
• ¹³⁰ Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX, USA.
• ¹³¹ Framingham Heart Study, Framingham, MA, USA.
• ¹³² University Medicine Greifswald, Institute for Community Medicine, SHIP/KEF, Greifswald, Germany.
• ¹³³ Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Washington, Seattle, WA, USA.
• ¹³⁴ Department of Veterans Affairs Office of Research and Development, Seattle Epidemiologic Research and Information Center, Seattle, WA, USA.
• ¹³⁵ Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
• ¹³⁶ Atlanta VA Health Care System, Decatur, GA, USA.
• ¹³⁷ Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA.
• ¹³⁸ Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Unviersity Hospital, Gothenburg, Sweden.
• ¹³⁹ Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
• ¹⁴⁰ Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
• ¹⁴¹ Division Heart & Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
• ¹⁴² Department of Neurology and Neurosurgery, University of Tartu, Tartu, Estonia.
• ¹⁴³ Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
• ¹⁴⁴ Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
• ¹⁴⁵ Department of Medicine, Division of Cardiovascular Disease, Emory University School of Medicine, Atlanta, GA, USA.
• ¹⁴⁶ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
• ¹⁴⁷ Division of Genome Science, Department of Precision Medicine, National Institute of Health, Cheongju, Republic of Korea.
• ¹⁴⁸ Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
• ¹⁴⁹ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
• ¹⁵⁰ German Center for Neurodegenerative Diseases (DZNE), site Rostock/Greifswald, Rostock, Germany.
• ¹⁵¹ Netherlands Heart Institute, Utrecht, The Netherlands.
• ¹⁵² Einthoven Laboratory for Experimental Vascular Medicine, LUMC, Leiden, The Netherlands.
• ¹⁵³ Department of Clinical Genetics, Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands.
• ¹⁵⁴ Latin American Brain Health (BrainLat), Universidad Adolfo Ibáñez, Santiago, Chile.
• ¹⁵⁵ Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY, USA.
• ¹⁵⁶ Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
• ¹⁵⁷ Department of Neurology, University of Virginia, Charlottesville, VA, USA.
• ¹⁵⁸ Department of Public Health Science, University of Virginia, Charlottesville, VA, USA.
• ¹⁵⁹ McGill Genome Centre, Montreal, Quebec, Canada.
• ¹⁶⁰ Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
• ¹⁶¹ Geisinger Neuroscience Institute, Geisinger Health System, Danville, PA, USA.
• ¹⁶² Department of Neurology, College of Medicine, The Pennsylvania State University, State College, PA, USA.
• ¹⁶³ Klinik für Neurologie, Carl von Ossietzky University of Oldenburg, Oldenburg, Germany.
• ¹⁶⁴ Comprehensive Heart Failure Center, University Hospital Würzburg, Würzburg, Germany.
• ¹⁶⁵ Clinical Trial Center, University Hospital Würzburg, Würzburg, Germany.
• ¹⁶⁶ Department of Neurology, University of Washington, Seattle, WA, USA.
• ¹⁶⁷ Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Republic of Korea.
• ¹⁶⁸ Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.
• ¹⁶⁹ Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada.
• ¹⁷⁰ Department of Surgery and Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA.
• ¹⁷¹ Corporal Michael Crescenz VA Medical Center, Philadelphia, PA, USA.
• ¹⁷² The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
• ¹⁷³ Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
• ¹⁷⁴ Division of Medicine, Turku University Hospital, Turku, Finland.
• ¹⁷⁵ Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
• ¹⁷⁶ Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
• ¹⁷⁷ Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan.
• ¹⁷⁸ Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
• ¹⁷⁹ Department of Medicine, University of Ibadan, Ibadan, Nigeria.
• ¹⁸⁰ Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany. [email protected].
• ¹⁸¹ Munich Cluster for Systems Neurology, Munich, Germany. [email protected].
• ¹⁸² German Center for Neurodegenerative Diseases (DZNE), Munich, Germany. [email protected].
• ¹⁸³ Bordeaux Population Health Research Center, University of Bordeaux, Inserm, UMR 1219, Bordeaux, France. [email protected].
• ¹⁸⁴ Department of Neurology, Institute for Neurodegenerative Diseases, CHU de Bordeaux, Bordeaux, France. [email protected].