title: Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease.
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.
authors: 1] Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA. [2].
authors: Mike A
authors: MA
authors: Nalls
authors: 1] Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA. [2].
authors: Nathan
authors: N
authors: Pankratz
authors: 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.
authors: Christina M
authors: CM
authors: Lill
authors: 23andMe, Inc., Mountain View, California, USA.
authors: Chuong B
authors: CB
authors: Do
authors: 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.
authors: Dena G
authors: DG
authors: Hernandez
authors: 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.
authors: Mohamad
authors: M
authors: Saad
authors: 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.
authors: Anita L
authors: AL
authors: DeStefano
authors: Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
authors: Eleanna
authors: E
authors: Kara
authors: Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
authors: Jose
authors: J
authors: Bras
authors: 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.
authors: Manu
authors: M
authors: Sharma
authors: Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
authors: Claudia
authors: C
authors: Schulte
authors: Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.
authors: Margaux F
authors: MF
authors: Keller
authors: Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.
authors: Sampath
authors: S
authors: Arepalli
authors: Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.
authors: Christopher
authors: C
authors: Letson
authors: Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.
authors: Connor
authors: C
authors: Edsall
authors: deCODE Genetics, Reykjavík, Iceland.
authors: Hreinn
authors: H
authors: Stefansson
authors: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA.
authors: Xinmin
authors: X
authors: Liu
authors: Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.
authors: Hannah
authors: H
authors: Pliner
authors: The Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, USA.
authors: Joseph H
authors: JH
authors: Lee
authors: The Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, USA.
authors: Rong
authors: R
authors: Cheng
authors: 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.
authors: M Arfan
authors: MA
authors: Ikram
authors: Stanford Prevention Research Center, Stanford University, Stanford, California, USA.
authors: John P A
authors: JP
authors: Ioannidis
authors: Neuroscience Unit, Department of Neurology, Faculty of Medicine, University of Thessaly, Larissa, Greece.
authors: Georgios M
authors: GM
authors: Hadjigeorgiou
authors: Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.
authors: Joshua C
authors: JC
authors: Bis
authors: 1] INSERM, UMR 1043, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, France. [2] Paul Sabatier University, Toulouse, France.
authors: Maria
authors: M
authors: Martinez
authors: 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.
authors: Joel S
authors: JS
authors: Perlmutter
authors: 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.
authors: Alison
authors: A
authors: Goate
authors: 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.
authors: Karen
authors: K
authors: Marder
authors: The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA.
authors: Brian
authors: B
authors: Fiske
authors: Neuroscience Center, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA.
authors: Margaret
authors: M
authors: Sutherland
authors: 1] Neuroscience Unit, Department of Neurology, Faculty of Medicine, University of Thessaly, Larissa, Greece. [2] Department of Neurology, Papageorgiou Hospital, Thessaloniki, Greece.
authors: Georgia
authors: G
authors: Xiromerisiou
authors: Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA.
authors: Richard H
authors: RH
authors: Myers
authors: 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.
authors: Lorraine N
authors: LN
authors: Clark
authors: deCODE Genetics, Reykjavík, Iceland.
authors: Kari
authors: K
authors: Stefansson
authors: Reta Lila Weston Institute, University College London Institute of Neurology, Queen Square, London, UK.
authors: John A
authors: JA
authors: Hardy
authors: Genome Biology for Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
authors: Peter
authors: P
authors: Heutink
authors: Epidemiology Branch, National Institute of Environmental Health Sciences, US National Institutes of Health, Research Triangle, North Carolina, USA.
authors: Honglei
authors: H
authors: Chen
authors: Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
authors: Nicholas W
authors: NW
authors: Wood
authors: Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
authors: Henry
authors: H
authors: Houlden
authors: New York State Department of Health Wadsworth Center, Albany, New York, USA.
authors: Haydeh
authors: H
authors: Payami
authors: 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.
authors: Alexis
authors: A
authors: Brice
authors: Department of Human Genetics, University of Miami School of Medicine, Miami, Florida, USA.
authors: William K
authors: WK
authors: Scott
authors: Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
authors: Thomas
authors: T
authors: Gasser
authors: 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.
authors: Lars
authors: L
authors: Bertram
authors: 23andMe, Inc., Mountain View, California, USA.
authors: Nicholas
authors: N
authors: Eriksson
authors: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors: Tatiana
authors: T
authors: Foroud
authors: Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.
authors: Andrew B
authors: AB
authors: Singleton
mesh_terms: D016022:Case-Control Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors