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Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.
Malik, Rainer; Chauhan, Ganesh; Traylor, Matthew; Sargurupremraj, Muralidharan; Okada, Yukinori; Mishra, Aniket; Rutten-Jacobs, Loes; Giese, Anne-Katrin; van der Laan, Sander W; Gretarsdottir, Solveig; Anderson, Christopher D; Chong, Michael; Adams, Hieab H H; Ago, Tetsuro; Almgren, Peter; Amouyel, Philippe; Ay, Hakan; Bartz, Traci M; Benavente, Oscar R; Bevan, Steve; Boncoraglio, Giorgio B; Brown, Robert D; Butterworth, Adam S; Carrera, Caty; Carty, Cara L; Chasman, Daniel I; Chen, Wei-Min; Cole, John W; Correa, Adolfo; Cotlarciuc, Ioana; Cruchaga, Carlos; Danesh, John; de Bakker, Paul I W; DeStefano, Anita L; den Hoed, Marcel; Duan, Qing; Engelter, Stefan T; Falcone, Guido J; Gottesman, Rebecca F; Grewal, Raji P; Gudnason, Vilmundur; Gustafsson, Stefan; Haessler, Jeffrey; Harris, Tamara B; Hassan, Ahamad; Havulinna, Aki S; Heckbert, Susan R; Holliday, Elizabeth G; Howard, George; Hsu, Fang-Chi.
Afiliação
  • Malik R; Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.
  • Chauhan G; Centre for Brain Research, Indian Institute of Science, Bangalore, India.
  • Traylor M; INSERM U1219 Bordeaux Population Health Research Center, University of Bordeaux, France.
  • Sargurupremraj M; Stroke Research Group, Division of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
  • Okada Y; Department of Neurology, Institute for Neurodegenerative Disease, Bordeaux University Hospital, Bordeaux, France.
  • Mishra A; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Rutten-Jacobs L; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan.
  • Giese AK; Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan.
  • van der Laan SW; Stroke Research Group, Division of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
  • Gretarsdottir S; Department of Neurology, Institute for Neurodegenerative Disease, Bordeaux University Hospital, Bordeaux, France.
  • Anderson CD; INSERM U1219 Bordeaux Population Health Research Center, University of Bordeaux, France.
  • Chong M; Department of Neurology, Massachusetts General Hospital (MGH), Harvard Medical School, Boston, MA, USA.
  • Adams HHH; Laboratory of Experimental Cardiology, Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands.
  • Ago T; deCODE genetics/AMGEN Inc., Reykjavik, Iceland.
  • Almgren P; Center for Genomic Medicine, MGH, Boston, MA, USA.
  • Amouyel P; J. Philip Kistler Stroke Research Center, Department of Neurology, MGH, Boston, MA, USA.
  • Ay H; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
  • Bartz TM; Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
  • Benavente OR; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
  • Bevan S; Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
  • Boncoraglio GB; Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Brown RD; Department of Clinical Sciences, Lund University, Malmö, Sweden.
  • Butterworth AS; INSERM, Institut Pasteur de Lille, LabEx DISTALZ-UMR1167, Risk Factors and Molecular Determinants of Aging-Related Diseases, Université Lille, Lille, France.
  • Carrera C; Centre Hospitalier Université Lille, Epidemiology and Public Health Department, Lille, France.
  • Carty CL; J. Philip Kistler Stroke Research Center, Department of Neurology, MGH, Boston, MA, USA.
  • Chasman DI; AA Martinos Center for Biomedical Imaging, Department of Radiology, MGH, Harvard Medical School, Boston, MA, USA.
  • Chen WM; Cardiovascular Health Research Unit, Departments of Biostatistics and Medicine, University of Washington, Seattle, WA, USA.
  • Cole JW; Division of Neurology, Faculty of Medicine, Brain Research Center, University of British Columbia, Vancouver, British Columbia, Canada.
  • Correa A; School of Life Science, University of Lincoln, Lincoln, UK.
  • Cotlarciuc I; Department of Cerebrovascular Diseases, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Milan, Italy.
  • Cruchaga C; Department of Neurology, Mayo Clinic Rochester, Rochester, MN, USA.
  • Danesh J; MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • de Bakker PIW; National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK.
  • DeStefano AL; Neurovascular Research Laboratory, Vall d'Hebron Institut of Research, Neurology and Medicine Departments-Universitat Autònoma de Barcelona, Vall d'Hebrón Hospital, Barcelona, Spain.
  • den Hoed M; Stroke Pharmacogenomics and Genetics, Fundacio Docència i Recerca MutuaTerrassa, Terrassa, Spain.
  • Duan Q; Children's Research Institute, Children's National Medical Center, Washington, DC, USA.
  • Engelter ST; Center for Translational Science, George Washington University, Washington, DC, USA.
  • Falcone GJ; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Gottesman RF; Harvard Medical School, Boston, MA, USA.
  • Grewal RP; Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
  • Gudnason V; Department of Neurology, University of Maryland School of Medicine and Baltimore VAMC, Baltimore, MD, USA.
  • Gustafsson S; Departments of Medicine, Pediatrics and Population Health Science, University of Mississippi Medical Center, Jackson, MS, USA.
  • Haessler J; Institute of Cardiovascular Research, Royal Holloway University of London, London, UK, and Ashford and St Peters Hospital, Surrey, UK.
  • Harris TB; Department of Psychiatry, Hope Center Program on Protein Aggregation and Neurodegeneration (HPAN), Washington University School of Medicine, St. Louis, MO, USA.
  • Hassan A; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA.
  • Havulinna AS; MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Heckbert SR; NIHR Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Holliday EG; Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
  • Howard G; British Heart Foundation, Cambridge Centre of Excellence, Department of Medicine, University of Cambridge, Cambridge, UK.
  • Hsu FC; Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
Nat Genet ; 50(4): 524-537, 2018 04.
Article em En | MEDLINE | ID: mdl-29531354
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Acidente Vascular Cerebral Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Female / Humans / Male Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Alemanha
Texto completo
Adicionar na Minha BVS
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XML
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Acidente Vascular Cerebral Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Female / Humans / Male Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Alemanha