Contribution of Common Genetic Variants to Risk of Early Onset Ischemic Stroke.


Journal

Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060

Informations de publication

Date de publication:
31 Aug 2022
Historique:
received: 05 10 2021
accepted: 09 06 2022
entrez: 14 10 2022
pubmed: 15 10 2022
medline: 15 10 2022
Statut: aheadofprint

Résumé

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 The

Sections du résumé

BACKGROUND AND OBJECTIVES OBJECTIVE
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.
METHODS METHODS
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.
RESULTS RESULTS
We observed genome-wide significant associations of EOS with two variants in
DISCUSSION CONCLUSIONS
The

Identifiants

pubmed: 36240095
pii: WNL.0000000000201006
doi: 10.1212/WNL.0000000000201006
pmc: PMC9620803
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Wellcome Trust
ID : 212946/Z/18/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12026/2
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : P30 AG028747
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS100178
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_00017/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U137686851
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : R01 NS114045
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL088521
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_14135
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL135129
Pays : United States
Organisme : Medical Research Council
ID : MR/S004130/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_13049
Pays : United Kingdom

Informations de copyright

© 2022 American Academy of Neurology.

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Auteurs

Thomas Jaworek (T)

Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA.

Huichun Xu (H)

Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA.

Brady J Gaynor (BJ)

Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA.

John W Cole (JW)

VA Maryland Health Care System.
Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA.

Kristiina Rannikmae (K)

Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, UK.

Tara M Stanne (TM)

Institute of Biomedicine, Department of Laboratory Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.

Liisa Tomppo (L)

Department of Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Vida Abedi (V)

Department of Molecular and Functional Genomics, Geisinger Health System, Danville, PA, USA.

Philippe Amouyel (P)

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.

Nicole D Armstrong (ND)

Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.

John Attia (J)

School of Medicine and Public Health, University of Newcastle and Hunter Medical Research Institute, Newcastle, Australia.

Steven Bell (S)

Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

Oscar R Benavente (OR)

Department of Neurology, University of British Columbia, Vancouver, British Columbia, Canada.

Giorgio B Boncoraglio (GB)

Department of Cerebrovascular Diseases, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Milan, Italy.

Jara Carcel-Marquez (J)

Stroke Pharmacogenomics and Genetics group, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.

Zhengming Chen (Z)

University of Oxford, UK; MRC Population Health Research Unit, University of Oxford, UK.

Michael Chong (M)

DBCVS Research Institute, Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
Thrombosis & Atherosclerosis Research Institute (TaARI).

Carlos Cruchaga (C)

Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.

Mary Cushman (M)

Department of Hematology and Oncology, University of Vermont, Medical Center, Colchester, USA.

John Danesh (J)

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.

Stephanie Debette (S)

INSERM U1219 Bordeaux Population Health Research Center, University of Bordeaux, France.
Department of Neurology, Institute for Neurodegenerative Disease, Bordeaux University Hospital, Bordeaux, France.

David J Duggan (DJ)

Quantitative Medicine and Systems Biology Division, Translational Genomics Research Institute, An Affiliate of City of Hope, Phoenix, AZ, USA.

Jon Peter Durda (JP)

Laboratory for Clinical Biochemistry Research, Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Colchester, VT, USA.

Gunnar Engstrom (G)

Department of Clinical Sciences, Malmö, Lund University, Sweden.

Chris Enzinger (C)

Department of Neurology, Medical University Graz, Austria.

Jessica D Faul (JD)

Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.

Natalie S Fecteau (NS)

Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA.

Israel Fernandez-Cadenas (I)

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.

Christian Gieger (C)

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.

Anne-Katrin Giese (AK)

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf.

Raji P Grewal (RP)

Neuroscience Institute, Saint Francis Medical Center, Trenton, New Jersey, USA.

Ulrike Grittner (U)

Department for Biostatistics and Clinical Epidemiology. Charité-University Medical Centre, Berlin, Germany.

Aki S Havulinna (AS)

National Institute for Health and Welfare, Helsinki, Finland.

Laura Heitsch (L)

Departments of Emergency Medicine and Neurology, Washington University School of Medicine, St. Louis, MO, USA.

Marc C Hochberg (MC)

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.

Elizabeth Holliday (E)

School of Medicine and Public Health, University of Newcastle and Hunter Medical Research Institute, Newcastle, Australia.

Jie Hu (J)

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.

Andreea Ilinca (A)

Department of Clinical Sciences Lund, Neurology, Lund University.
Department of Neurology and Rehabilitation Medicine, Skane University Hospital, Lund, Sweden.

Marguerite R Irvin (MR)

Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.

Rebecca D Jackson (RD)

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.

Mina A Jacob (MA)

Department of Neurology, Radboud University Medical Center; Donders Medical Center for Neuroscience; Nijmegen, The Netherlands.

Jordi Jimenez-Conde (J)

Neurovascular Research Group (NEUVAS), Neurology Department, Institut Hospital del Mar d'Investigacio Medica, Universitat Autonoma de Barcelona, Barcelona, Spain.

Julie A Johnson (JA)

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.

Yoichiro Kamatani (Y)

Laboratory of Complex Trait Genomics, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.

Sharon L Kardia (SL)

Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI USA.

Masaru Koido (M)

Department of Cancer Biology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Michiaki Kubo (M)

RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.

Leslie Lange (L)

Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.

Jin-Moo Lee (JM)

Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.

Robin Lemmens (R)

KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology; VIB Center; For Brain & Disease Research.
University Hospitals Leuven, Department of Neurology, Leuven, Belgium.

Christopher R Levi (CR)

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.

Jiang Li (J)

Department of Molecular and Functional Genomics, Geisinger Health System, Danville, PA, USA.

Liming Li (L)

Peking University Health Science Center, Department of Epidemiology and Biostatistics, Peking University, Beijing, China.

Kuang Lin (K)

University of Oxford, UK; MRC Population Health Research Unit, University of Oxford, UK.

Haley Lopez (H)

Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA.

Sothear Luke (S)

Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.

Jane Maguire (J)

Faculty of Health, School of Nursing and Midwifery, University of Technology Sydney, NSW, Australia.

Patrick F McArdle (PF)

Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA.

Caitrin W McDonough (CW)

Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, College of Pharmacy, Gainesville, FL, USA.

James F Meschia (JF)

Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.

Tiina Metso (T)

Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.

Martina Muller-Nurasyid (M)

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.

Timothy D O'Connor (TD)

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.

Martin O'Donnell (M)

Health Research Board Clinical Research Facility, Geata an Eolais, National University of Ireland, Galway, Ireland.

Leema R Peddareddygari (LR)

Neuroscience Institute, Saint Francis Medical Center, Trenton, New Jersey, USA.

Joanna Pera (J)

Department of Neurology, Jagiellonian University, Botaniczna 3, 31-503 Krakow, Poland.

James A Perry (JA)

Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA.

Annette Peters (A)

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.

Jukka Putaala (J)

Department of Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Debashree Ray (D)

Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.

Kathryn Rexrode (K)

Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.

Peter M Rothwell (PM)

University of Oxford, UK; MRC Population Health Research Unit, University of Oxford, UK.

Tatjana Rundek (T)

Department of Neurology and Evelin F. McKnight Brain Institute, Miller School of Medicine, University of Miami, Miami, FL, USA.

Kathleen A Ryan (KA)

Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA.

Ralph L Sacco (RL)

Department of Neurology and Evelin F. McKnight Brain Institute, Miller School of Medicine, University of Miami, Miami, FL, USA.

Veikko Salomaa (V)

National Institute for Health and Welfare, Helsinki, Finland.

Cristina Sanchez-Mora (C)

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.

Reinhold Schmidt (R)

Department of Neurology, Medical University Graz, Austria.

Pankaj Sharma (P)

Institute of Cardiovascular Research, Royal Holloway University of London, London, UK, and Ashford and St. Peters Hospital, Surrey, UK.

Agnieszka Slowik (A)

Department of Neurology, Jagiellonian University, Botaniczna 3, 31-503 Krakow, Poland.

Jennifer A Smith (JA)

Department of Clinical Sciences, Malmö, Lund University, Sweden.

Sylvia Wassertheil-Smoller (S)

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY, USA.

Martin Soederholm (M)

Department of Clinical Sciences, Malmö, Lund University, Sweden.
Department of Clinical Sciences Lund, Neurology, Lund University.

O C Stine (OC)

Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA.

Daniel Strbian (D)

Department of Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Cathie L Sudlow (CL)

Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, UK.
BHF Data Science Centre, Health Data Research UK, London, UK.

Turgut Tatlisumak (T)

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.

Chikashi Terao (C)

RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.

Vincent Thijs (V)

Stroke Theme, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Heidelberg, Victoria, Australia; Department of Neurology, Austin Health, Heidelberg, Victoria, Australia.

Nuria P Torres-Aguila (NP)

Stroke Pharmacogenomics and Genetics group, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.

David-Alexandre Tregouet (DA)

INSERM U1219 Bordeaux Population Health Research Center, University of Bordeaux, France.

Anil M Tuladhar (AM)

Department of Neurology, Radboud University Medical Center; Donders Medical Center for Neuroscience; Nijmegen, The Netherlands.

Jan H Veldink (JH)

Department of Neurology, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands.

Robin G Walters (RG)

University of Oxford, UK; MRC Population Health Research Unit, University of Oxford, UK.

David R Weir (DR)

Department of Clinical Sciences, Malmö, Lund University, Sweden.

Daniel Woo (D)

Department of Neurology and Rehabilitation Medicine; University of Cincinnati College of Medicine; Cincinnati, OH, USA.

Bradford B Worrall (BB)

Departments of Neurology and Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA.

Charles C Hong (CC)

Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA.

Owen Ross (O)

Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.

Ramin Zand (R)

Department of Molecular and Functional Genomics, Geisinger Health System, Danville, PA, USA.

Frank-Erik de Leeuw (FE)

Department of Neurology, Radboud University Medical Center; Donders Medical Center for Neuroscience; Nijmegen, The Netherlands.

Arne G Lindgren (AG)

Department of Clinical Sciences Lund, Neurology, Lund University.
Section of Neurology, Skåne University Hospital, Lund, Sweden.

Guillaume Pare (G)

DBCVS Research Institute, Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
Thrombosis & Atherosclerosis Research Institute (TaARI).

Christopher D Anderson (CD)

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.

Hugh S Markus (HS)

Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

Christina Jern (C)

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.

Rainer Malik (R)

Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.

Braxton D Mitchell (BD)

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.

Steven J Kittner (SJ)

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.

Classifications MeSH