Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/31042
Title: Contribution of Common Genetic Variants to Risk of Early Onset Ischemic Stroke.
Austin Authors: Jaworek, Thomas;Xu, Huichun;Gaynor, Brady J;Cole, John W;Rannikmae, Kristiina;Stanne, Tara M;Tomppo, Liisa;Abedi, Vida;Amouyel, Philippe;Armstrong, Nicole D;Attia, John;Bell, Steven;Benavente, Oscar R;Boncoraglio, Giorgio B;Butterworth, Adam;Carcel-Marquez, Jara;Chen, Zhengming;Chong, Michael;Cruchaga, Carlos;Cushman, Mary;Danesh, John;Debette, Stephanie;Duggan, David J;Durda, Jon Peter;Engstrom, Gunnar;Enzinger, Chris;Faul, Jessica D;Fecteau, Natalie S;Fernandez-Cadenas, Israel;Gieger, Christian;Giese, Anne-Katrin;Grewal, Raji P;Grittner, Ulrike;Havulinna, Aki S;Heitsch, Laura;Hochberg, Marc C;Holliday, Elizabeth;Hu, Jie;Ilinca, Andreea;Irvin, Marguerite R;Jackson, Rebecca D;Jacob, Mina A;Janssen, Raquel Rabionet;Jimenez-Conde, Jordi;Johnson, Julie A;Kamatani, Yoichiro;Kardia, Sharon L;Koido, Masaru;Kubo, Michiaki;Lange, Leslie;Lee, Jin-Moo;Lemmens, Robin;Levi, Christopher R;Li, Jiang;Li, Liming;Lin, Kuang;Lopez, Haley;Luke, Sothear;Maguire, Jane;McArdle, Patrick F;McDonough, Caitrin W;Meschia, James F;Metso, Tiina;Muller-Nurasyid, Martina;O'Connor, Timothy D;O'Donnell, Martin;Peddareddygari, Leema R;Pera, Joanna;Perry, James A;Peters, Annette;Putaala, Jukka;Ray, Debashree;Rexrode, Kathryn;Ribases, Marta;Rosand, Jonathan;Rothwell, Peter M;Rundek, Tatjana;Ryan, Kathleen A;Sacco, Ralph L;Salomaa, Veikko;Sanchez-Mora, Cristina;Schmidt, Reinhold;Sharma, Pankaj;Slowik, Agnieszka;Smith, Jennifer A;Smith, Nicholas L;Wassertheil-Smoller, Sylvia;Soederholm, Martin;Stine, O C;Strbian, Daniel;Sudlow, Cathie L;Tatlisumak, Turgut;Terao, Chikashi;Thijs, Vincent N ;Torres-Aguila, Nuria P;Tregouet, David-Alexandre;Tuladhar, Anil M;Veldink, Jan H;Walters, Robin G;Weir, David R;Woo, Daniel;Worrall, Bradford B;Hong, Charles C;Ross, Owen;Zand, Ramin;Leeuw, Frank-Erik de;Lindgren, Arne G;Pare, Guillaume;Anderson, Christopher D;Markus, Hugh S;Jern, Christina;Malik, Rainer;Dichgans, Martin;Mitchell, Braxton D;Kittner, Steven J
Affiliation: Neurology
Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA.
School of Medicine and Public Health, University of Newcastle and Hunter Medical Research Institute, Newcastle, Australia
The Florey Institute of Neuroscience and Mental Health
Faculty of Health, School of Nursing and Midwifery, University of Technology Sydney, NSW, Australia
John Hunter Hospital, Hunter Medical Research Institute and University of Newcastle, Newcastle, Australia and Priority Research Centre for Stroke & Brain Injury, University of Newcastle, NSW, Australia
Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA..
VA Maryland Health Care System.. Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA..
Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, UK.
Institute of Biomedicine, Department of Laboratory Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden..
Department of Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland..
Department of Molecular and Functional Genomics, Geisinger Health System, Danville, PA, USA..
LabEx DISTALZ-U1167, RID-AGE-Risk Factors and Molecular Determinants of Aging-Related Diseases, University of Lille, Lille, France; Inserm U1167, Lille, France.. Centre Hospitalier Universitaire Lille, Lille, France; Institut Pasteur de Lille, Lille, France..
Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA..
Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK..
Department of Neurology, University of British Columbia, Vancouver, British Columbia, Canada..
Department of Cerebrovascular Diseases, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Milan, Italy..
Stroke Pharmacogenomics and Genetics group, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain..
University of Oxford, UK; MRC Population Health Research Unit, University of Oxford, UK..
DBCVS Research Institute, Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.. Thrombosis & Atherosclerosis Research Institute (TaARI)..
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA..
Department of Hematology and Oncology, University of Vermont, Medical Center, Colchester, USA..
British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.. Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK.. Department of Human Genetics, Wellcome Sanger Institute, Hinxton, UK..
INSERM U1219 Bordeaux Population Health Research Center, University of Bordeaux, France.. Department of Neurology, Institute for Neurodegenerative Disease, Bordeaux University Hospital, Bordeaux, France..
Quantitative Medicine and Systems Biology Division, Translational Genomics Research Institute, An Affiliate of City of Hope, Phoenix, AZ, USA..
Laboratory for Clinical Biochemistry Research, Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Colchester, VT, USA..
Department of Clinical Sciences, Malmö, Lund University, Sweden.
Department of Neurology, Medical University Graz, Austria.
Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA..
Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA..
Stroke Pharmacogenomics and Genetics group, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.. Stroke Pharmacogenomics and Genetics, Fundacio Docència i Recerca MutuaTerrassa, Terrassa, Spain..
Institute of Epidemiology, Helmholtz Zentrum München German Research Center for Environmental Health, Neuherberg, Germany.. Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München German Research Center for Environmental Health, Ingolstaedter Landstraße 1, 85764, Neuherberg, Germany..
Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf..
Neuroscience Institute, Saint Francis Medical Center, Trenton, New Jersey, USA..
Department for Biostatistics and Clinical Epidemiology. Charité-University Medical Centre, Berlin, Germany..
National Institute for Health and Welfare, Helsinki, Finland.
Departments of Emergency Medicine and Neurology, Washington University School of Medicine, St. Louis, MO, USA..
Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.. Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA..
Division of Women's Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA..
Department of Clinical Sciences Lund, Neurology, Lund University.. Department of Neurology and Rehabilitation Medicine, Skane University Hospital, Lund, Sweden..
Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA..
Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine and the Center for Clinical and Translational Science, The Ohio State University, Columbus, OH, USA..
Department of Neurology, Radboud University Medical Center; Donders Medical Center for Neuroscience; Nijmegen, The Netherlands..
Neurovascular Research Group (NEUVAS), Neurology Department, Institut Hospital del Mar d'Investigacio Medica, Universitat Autonoma de Barcelona, Barcelona, Spain..
Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, College of Pharmacy, Gainesville, FL, USA.. Division of Cardiovascular Medicine, College of Medicine, University of Florida, Gainesville, FL, USA..
Laboratory of Complex Trait Genomics, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan..
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI USA..
Department of Cancer Biology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan..
RIKEN Center for Integrative Medical Sciences, Yokohama, Japan..
Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA..
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA..
KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology; VIB Center; For Brain & Disease Research.. University Hospitals Leuven, Department of Neurology, Leuven, Belgium..
Department of Molecular and Functional Genomics, Geisinger Health System, Danville, PA, USA..
Peking University Health Science Center, Department of Epidemiology and Biostatistics, Peking University, Beijing, China..
University of Oxford, UK; MRC Population Health Research Unit, University of Oxford, UK..
Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA..
Department of Neurology, Mayo Clinic, Jacksonville, FL, USA..
Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA..
Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, College of Pharmacy, Gainesville, FL, USA..
Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland..
Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany Department of Medicine I, Ludwig-Maximilians University Munich, Munich, Germany..
Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA.. Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA..
Health Research Board Clinical Research Facility, Geata an Eolais, National University of Ireland, Galway, Ireland..
Neuroscience Institute, Saint Francis Medical Center, Trenton, New Jersey, USA.
Department of Neurology, Jagiellonian University, Botaniczna 3, 31-503 Krakow, Poland.
Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA..
Institute of Epidemiology, Helmholtz Zentrum München German Research Center for Environmental Health, Neuherberg, Germany.. Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig-Maximilians-University, Munich, Germany..
Department of Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland..
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA..
Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA..
University of Oxford, UK; MRC Population Health Research Unit, University of Oxford, UK..
Department of Neurology and Evelin F. McKnight Brain Institute, Miller School of Medicine, University of Miami, Miami, FL, USA..
Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA..
Department of Neurology and Evelin F. McKnight Brain Institute, Miller School of Medicine, University of Miami, Miami, FL, USA..
National Institute for Health and Welfare, Helsinki, Finland.
Psychiatric Genetics Unit, Group of Psychiatry, Mental Health and Addiction, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.. Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain..
Institute of Cardiovascular Research, Royal Holloway University of London, London, UK, and Ashford and St. Peters Hospital, Surrey, UK..
Department of Neurology, Jagiellonian University, Botaniczna 3, 31-503 Krakow, Poland..
Department of Clinical Sciences, Malmö, Lund University, Sweden..
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY, USA..
Department of Clinical Sciences, Malmö, Lund University, Sweden.. Department of Clinical Sciences Lund, Neurology, Lund University..
Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA..
Department of Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland..
Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, UK.. BHF Data Science Centre, Health Data Research UK, London, UK..
Department of Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.. Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.. Department of Clinical Neuroscience, Institute of Neurosciences and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden..
RIKEN Center for Integrative Medical Sciences, Yokohama, Japan..
Stroke Pharmacogenomics and Genetics group, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain..
INSERM U1219 Bordeaux Population Health Research Center, University of Bordeaux, France..
Department of Neurology, Radboud University Medical Center; Donders Medical Center for Neuroscience; Nijmegen, The Netherlands..
Department of Neurology, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands..
University of Oxford, UK; MRC Population Health Research Unit, University of Oxford, UK..
Department of Clinical Sciences, Malmö, Lund University, Sweden..
Department of Neurology and Rehabilitation Medicine; University of Cincinnati College of Medicine; Cincinnati, OH, USA..
Departments of Neurology and Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA..
Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA..
Department of Neurology, Mayo Clinic, Jacksonville, FL, USA..
Department of Molecular and Functional Genomics, Geisinger Health System, Danville, PA, USA..
Department of Neurology, Radboud University Medical Center; Donders Medical Center for Neuroscience; Nijmegen, The Netherlands..
Department of Clinical Sciences Lund, Neurology, Lund University.. Section of Neurology, Skåne University Hospital, Lund, Sweden..
DBCVS Research Institute, Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.. Thrombosis & Atherosclerosis Research Institute (TaARI)..
McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA, USA.. Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA..
Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK..
Institute of Biomedicine, Department of Laboratory Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.. Region Vastra Gotaland, Sahlgrenska University Hospital, Department of Clinical Genetics and Genomics, Gothenburg, Sweden..
Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany..
Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA bmitchel@som.umaryland.edu.. Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, MD, USA..
Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA.. Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, MD, USA..
Issue Date: 31-Aug-2022
Date: 2022
Publication information: Neurology 2022-10-17; 99(16)
Abstract: Current genome-wide association studies of ischemic stroke have focused primarily on late onset disease. As a complement to these studies, we sought to identifythe contribution of common genetic variants to risk of early onset ischemic stroke. We performed a meta-analysis of genome-wide association studies of early onset stroke (EOS), ages 18-59, using individual level data or summary statistics in 16,730 cases and 599,237 non-stroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late onset stroke (LOS) and compared polygenic risk scores for venous thromboembolism between EOS and LOS. We observed genome-wide significant associations of EOS with two variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared to LOS. The odds ratio (OR) for rs529565, tagging O1, 0.88 (95% CI: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using polygenic risk scores, we observed that greater genetic risk for venous thromboembolism, another prothrombotic condition, was more strongly associated with EOS compared to LOS (p=0.008). The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.
URI: https://ahro.austin.org.au/austinjspui/handle/1/31042
DOI: 10.1212/WNL.0000000000201006
ORCID: https://orcid.org/0000-0002-4142-0613
https://orcid.org/0000-0001-9263-8930
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https://orcid.org/0000-0002-0654-387X
Journal: Neurology
PubMed URL: 36240095
Type: Journal Article
Appears in Collections:Journal articles

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