학술논문

Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease.
Document Type
Academic Journal
Author
Nalls MA; 1] Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA. [2].; Pankratz N; 1] Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA. [2].; Lill CM; 1] Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany. [2] Department of Neurology, Focus Program Translational Neuroscience, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.; Do CB; 23andMe, Inc., Mountain View, California, USA.; Hernandez DG; 1] Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA. [2] Reta Lila Weston Institute, University College London Institute of Neurology, Queen Square, London, UK.; Saad M; 1] Department of Biostatistics, University of Washington, Seattle, Washington, USA. [2] INSERM, UMR 1043, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, France. [3] Paul Sabatier University, Toulouse, France.; DeStefano AL; 1] Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA. [2] Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA. [3] National Heart, Lung, and Blood Institute (NHLBI) Framingham Heart Study, Framingham, Massachusetts, USA.; Kara E; Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.; Bras J; Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.; Sharma M; 1] Institute for Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany. [2] Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.; Schulte C; Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.; Keller MF; Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.; Arepalli S; Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.; Letson C; Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.; Edsall C; Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.; Stefansson H; deCODE Genetics, Reykjavík, Iceland.; Liu X; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA.; Pliner H; Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.; Lee JH; The Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, USA.; Cheng R; The Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, USA.; Ikram MA; 1] Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands. [2] Department of Radiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands. [3] Department of Neurology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.; Ioannidis JP; Stanford Prevention Research Center, Stanford University, Stanford, California, USA.; Hadjigeorgiou GM; Neuroscience Unit, Department of Neurology, Faculty of Medicine, University of Thessaly, Larissa, Greece.; Bis JC; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.; Martinez M; 1] INSERM, UMR 1043, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, France. [2] Paul Sabatier University, Toulouse, France.; Perlmutter JS; 1] Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA. [2] Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA. [3] Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.; Goate A; 1] Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA. [2] Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA. [3] Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA. [4] Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA.; Marder K; 1] The Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, USA. [2] Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, New York, USA. [3] Department of Neurology, Columbia University Medical Center, New York, New York, USA. [4] Department of Psychiatry, Columbia University Medical Center, New York, New York, USA.; Fiske B; The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA.; Sutherland M; Neuroscience Center, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA.; Xiromerisiou G; 1] Neuroscience Unit, Department of Neurology, Faculty of Medicine, University of Thessaly, Larissa, Greece. [2] Department of Neurology, Papageorgiou Hospital, Thessaloniki, Greece.; Myers RH; Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA.; Clark LN; 1] Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA. [2] The Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, USA.; Stefansson K; deCODE Genetics, Reykjavík, Iceland.; Hardy JA; Reta Lila Weston Institute, University College London Institute of Neurology, Queen Square, London, UK.; Heutink P; Genome Biology for Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.; Chen H; Epidemiology Branch, National Institute of Environmental Health Sciences, US National Institutes of Health, Research Triangle, North Carolina, USA.; Wood NW; Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.; Houlden H; Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.; Payami H; New York State Department of Health Wadsworth Center, Albany, New York, USA.; Brice A; 1] Sorbonne Université, UPMC Université Paris 06, UM 75, INSERM U1127, Institut du Cerveau et de la Moelle, Paris, France. [2] CNRS, UMR 7225, Paris, France. [3] Pitié-Salpêtrière Hospital, Department of Genetics and Cytogenetics, Paris, France.; Scott WK; Department of Human Genetics, University of Miami School of Medicine, Miami, Florida, USA.; Gasser T; Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.; Bertram L; 1] Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany. [2] School of Public Health, Faculty of Medicine, The Imperial College of Science, Technology and Medicine, London, UK.; Eriksson N; 23andMe, Inc., Mountain View, California, USA.; Foroud T; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.; Singleton AB; Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.
Source
Publisher: Nature Pub. Co Country of Publication: United States NLM ID: 9216904 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-1718 (Electronic) Linking ISSN: 10614036 NLM ISO Abbreviation: Nat Genet Subsets: MEDLINE
Subject
Language
English
Abstract
We conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as having genome-wide significant association; these and 6 additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 newly identified loci. Conditional analyses within loci showed that four loci, including GBA, GAK-DGKQ, SNCA and the HLA region, contain a secondary independent risk variant. In total, we identified and replicated 28 independent risk variants for Parkinson's disease across 24 loci. Although the effect of each individual locus was small, risk profile analysis showed substantial cumulative risk in a comparison of the highest and lowest quintiles of genetic risk (odds ratio (OR) = 3.31, 95% confidence interval (CI) = 2.55-4.30; P = 2 × 10(-16)). We also show six risk loci associated with proximal gene expression or DNA methylation.