Accepted for Publication: February 20, 2013.
Published Online: August 5, 2013. doi:10.1001/jamaneurol.2013.448.
Acquisition of data: Bras, Simón-Sánchez, Gibbs, Schulte, Durr, Guerreiro, Hernandez, Stefánsson, Majamaa, Gasser, Heutink, Martinez, Singleton, Nalls, Hardy, O’Donovan, J. Williams, N. M. Williams.
Analysis and interpretation of data: Moskvina, Harold, Russo, Vedernikov, Sharma, Saad, Holmans, Bettella, Keller, Nicolaou, Gibbs, Gasser, Nalls, Owen, O’Donovan, J. Williams, N. M. Williams.
Drafting of the manuscript: Moskvina, Harold, Vedernikov, Durr, Hernandez, Brice, Hardy, J. Williams, Morris, N. M. Williams.
Critical revision of the manuscript for important intellectual content: Moskvina, Russo, Sharma, Saad, Holmans, Bras, Bettella, Keller, Nicolaou, Simón-Sánchez, Gibbs, Schulte, Guerreiro, Stefánsson, Majamaa, Gasser, Heutink, Wood, Martinez, Singleton, Nalls, Owen, O’Donovan, J. Williams, Morris, N. M. Williams.
Statistical analysis: Moskvina, Harold, Russo, Vedernikov, Sharma, Saad, Holmans, Bettella, Keller, Nicolaou, Gibbs, Schulte, Nalls, O’Donovan, J. Williams.
Obtained funding: Sharma, Heutink, Wood, Martinez, Singleton, Nalls, Hardy, Owen, O’Donovan, J. Williams, Morris, N. M. Williams.
Administrative, technical, and material support: Vedernikov, Gibbs, Hernandez, Gasser, Martinez, Owen, O’Donovan, J. Williams, N. M. Williams.
Study supervision: Moskvina, Gasser, Wood, Singleton, Nalls, Hardy, Owen, O’Donovan, J. Williams, Morris, N. M. Williams.
Conflict of Interest Disclosures: None reported.
Funding/Support: This work was supported by Parkinson’s United Kingdom (formerly The PD society; reference K0906; grants 8047 and J-0804) and the Medical Research Council (grant G0700943). In addition, part of the study was undertaken at the University College Hospital/University College London (UCL) using funding from the Department of Health National Institute for Health Research Biomedical Research Centre. The German work was also supported by the German National Genome Network (plus grant 01GS08134 from the German Ministry for Education and Research). This work was also supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services (projects Z01 AG000949-06 and Z01 AG000950-10). The French GWA scan work was supported by the French National Agency of Research (www.agence-nationale-recherche.fr; grant ANR-08-MNP-012) and by the National Research Funding Agency (grant ANR-08-NEUR-004-01) in the ERA-NET NEURON framework (www.neuron-eranet.eu).
Group Information for IPDGC Investigators: The investigator were Allissa Dillman, Dena G. Hernandez, Janet Brooks, Sean Chong, Mark R. Cookson, J. Raphael Gibbs, Matthew Moore, Margaux F. Keller, Michael A. Nalls, Andrew B. Singleton, Bryan J. Traynor, and Sampath Arepalli, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland; Gavin Charlesworth and Vincent Plagnol, UCL Genetics Institute, London, England; Mina Ryten, Daniah Trabzuni, Rita Guerreiro, Dena G. Hernandez, Jose M. Bras, J. Raphael Gibbs, and John Hardy, Department of Molecular Neuroscience and Reta Lila Weston Laboratories, Institute of Neurology, UCL, London, England; Claudia Schulte, Daniela Berg, Kathrin Brockmann, Thomas Gasser, Heiko Huber, and Manu Sharma, Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, and German Center for Neurodegenerative Diseases, Tübingen, Germany; Una-Marie Sheerin and Kailash Bhatia, UCL Institute of Neurology, London, England; Maria Martinez and Mohamad Saad, INSERM U563, Centre de Physiopathologie de Toulouse–Purpan, and Paul Sabatier University, Toulouse, France; Javier Simón-Sánchez, Zoltan Bochdanovits, Peter Heutink, and Patrizia Rizzu, Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Centre, Amsterdam, the Netherlands; Suzanne Lesage, Marie Vidailhet, Alexis Brice, and Jen-Christophe Corvol, INSERM, UMR S975 (formerly UMR S679), and Université Pierre et Marie Curie, Paris, France; Roger Barker, Department of Neurology, Addenbrooke’s Hospital, University of Cambridge, England; Sarah E. Hunt, Emma Gray, Sarah Edkins, Avazeh Tashakkori-Ghanbaria, Jeffrey Barrett, Panagiotis Deloukasm, and Simon Potter, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, England; Yoav Ben-Shlomo, Department of Social Medicine, Bristol University, England; Karin D. van Dijk and Henk W. Berendse, Department of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands; Daan Velseboer and Rob M. A. de Bie, Department of Neurology, Academic Medical Center, University of Amsterdam, the Netherlands; Alessandro Biffi, Center for Human Genetic Research and Department of Neurology, Massachusetts General Hospital, Boston, and Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts; Bas Bloem, Bart van de Warrenburg, and Bart Post, Department of Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands; Olaf Riess and Michael Bonin, Department of Medical Genetics, Institute of Human Genetics, University of Tübingen, Germany; David J. Burn, Newcastle University Clinical Ageing Research Unit, Campus for Ageing and Vitality, England; Jianjun Gao and Honglei Chen, Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina; Gavin Hudson and Patrick F. Chinnery, Neurology, The Medical School, Newcastle upon Tyne, England; Karen E. Morrison, Catriona Moorby, Joanna D. Stockton, and Carl E. Clarke, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, England; Anthony Schapira, Jonathan M. Cooper, and Alisdair McNeill, Department of Clinical Neurosciences, UCL Institute of Neurology, Royal Free Campus, London, England; Jen-Christophe Corvol, INSERM CIC 9503, Hôpital Pitié-Salpêtrière, Paris, France; Clare Harris and Carl Counsell, University of Aberdeen, Division of Applied Health Sciences, Population Health Section, Foresterhill, England; Philippe Damier, CHU Nantes, CIC 0004, Service de Neurologie, Nantes, France; Jean Francois Dartigues, INSERM U897, Victor Segalen University, Bordeaux, France; Delia Lorenz and Günther Deuschl, Klinik für Neurologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Christian-Albrechts-Universität Kiel, Germany; David T. Dexter, Parkinson’s Disease Research Group, Faculty of Medicine, Imperial College London, Hammersmith Hospital, England; Frank Durif, Service de Neurologie, Hôpital Gabriel Montpied, Clermont-Ferrand, France; Alexandra Durr and Alexis Brice, Assistance Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Department of Genetics and Cytogenetics, France; Caroline H. Williams-Gray, Cordelia Langford, and Jonathan R. Evans, Cambridge Centre for Brain Repair, England; Michelle Gardner, Thomas Foltynie, and Nicholas Wood, Institute of Neurology, UCL, London, England; Alison Goate and Joel S. Perlmutter, Departments of Psychiatry and Neurology, Washington University School of Medicine, St Louis, Missouri; Stacy Steinberg, Kári Stefánsson, Johanna Huttenlocher, Ómar Gústafsson, Hjörvar Pétursson, and Hreinn Stefánsson, deCODE Genetics, Reykjavik, Iceland; Jacobus J. van Hilten, Department of Neurology, Leiden University Medical Center, the Netherlands; Albert Hofman, Fernando Rivadeneira, and André G. Uitterlinden, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands; Albert Hollenbeck, American Association of Retired Persons, Washington, DC; Karen Shaw, Janice Holton, Andrew Lees, and Tamas Revesz, Queen Square Brain Bank for Neurological Disorders, Institute of Neurology, UCL, London, England; Michele Hu, Department of Clinical Neurology, John Radcliffe Hospital, Oxford, England; Thomas Illig, Institute of Epidemiology, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Germany; Peter Lichtner, Institute of Human Genetics, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Germany; Patricia Limousin, Institute of Neurology, Sobell Department, Unit of Functional Neurosurgery, London, England; Ellen Sidransky and Grisel Lopez, Section on Molecular Neurogenetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland; Valentina Moskvina, Nigel Williams, Peter Holmans, Huw Morris, and Justin Pearson, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Wales; Ese Mudanohwo, Neurogenetics Unit, UCL Institute of Neurology/National Hospital for Neurology and Neurosurgery, London, England; Pierre Pollak, Service de Neurologie, CHU de Grenoble, France; Bernard Ravina, Translational Neurology, Biogen Idec, Cambridge, Massachusetts; Fernando Rivadeneira, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands; Stephen Sawcer, University of Cambridge, Department of Clinical Neurosciences, Addenbrooke’s Hospital, England; Hans Scheffer, Department of Human Genetics, Radboud University Nijmegen Medical Centre, the Netherlands; Ira Shoulson, Department of Neurology, University of Rochester, New York; Robert Walker and Colin Smith, Department of Pathology, University of Edinburgh, Scotland; Sigurlaug Sveinbjornsdottir, Department of Neurology, Landspítali, University Hospital, Reykjavík, Iceland; Kevin Talbot, University of Oxford, Department of Clinical Neurology, John Radcliffe Hospital, England; Carlie M. Tanner, Clinical Research Department, The Parkinson’s Institute and Clinical Center, Sunnyvale, California; François Tison, Service de Neurologie, Hôpital Haut-Lévêque, Pessac, France; Mirdhu Wickremaratchi, Department of Neurology, Cardiff University, Wales; and Sophie Winder-Rhodes, Department of Psychiatry and Medical Research Council/Wellcome Trust Behavioural and Clinical Neurosciences Institute, University of Cambridge, England.
Group Information for GERAD Investigators: The investigators were Denise Harold, Rebecca Sims, Amy Gerrish, Jade Chapman, Valentina Moskvina, Marian Hamshere, Kimberley Dowzell, Amy Williams, Nicola Jones, Charlene Thomas, Alexandra Stretton, Peter Holmans, Michael O’Donovan, Michael J. Owen, Richard Abraham, Paul Hollingworth, Jaspreet Singh Pahwa, Julie Williams, and Angharad Morgan, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Neurosciences and Mental Health Research Institute, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Wales; Petroula Proitsi, Michelle K. Lupton, Simon Lovestone, and John Powell, Department of Neuroscience, Institute of Psychiatry, Kings College London, England; Carol Brayne, Institute of Public Health, University of Cambridge, England; David C. Rubinsztein, Cambridge Institute for Medical Research, University of Cambridge, England; Michael Gill, Brian Lawlor, and Aoibhinn Lynch, Mercer’s Institute for Research on Aging, St James Hospital and Trinity College, Dublin, Ireland; Kristelle Brown and Kevin Morgan, Institute of Genetics, Queen’s Medical Centre, University of Nottingham, England; Bernadette McGuinness, Stephen Todd, Peter Passmore, and David Craig, Ageing Group, Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Northern Ireland; Clive Holmes, Division of Clinical Neurosciences, School of Medicine, University of Southampton, England; David Mann, Clinical Neuroscience Research Group, Greater Manchester Neurosciences Centre, University of Manchester, Salford, England; A. David Smith, Oxford Project to Investigate Memory and Ageing, University of Oxford, Level 4, John Radcliffe Hospital, England; Seth Love and Patrick G. Kehoe, Dementia Research Group, University of Bristol Institute of Clinical Neurosciences, Frenchay Hospital, England; John Hardy, Department of Molecular Neuroscience and Reta Lilla Weston Laboratories, Institute of Neurology, London, England; Simon Mead and John Collinge, Medical Research Council Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, London, England; Nick Fox and Martin Rossor, Dementia Research Centre, Department of Neurodegenerative Diseases, UCL, Institute of Neurology, London, England; Britta Schürmann, Wolfgang Maier, Frank Jessen, Reiner Heun, Heike Kölsch, and Alfredo Ramirez, Department of Psychiatry, University of Bonn, Germany; Britta Schürmann, Institute for Molecular Psychiatry, University of Bonn, Germany; Hendrik van den Bussche, Institute of Primary Medical Care, University Medical Center Hamburg-Eppendorf, Germany; Isabella Heuser, Department of Psychiatry, Charité-Universitätsmedizin Berlin, Germany; Johannes Kornhuber, Department of Psychiatry, University of Erlangen, Nürnberg, Germany; Jens Wiltfang, LVR-Hospital Essen, Department of Psychiatry and Psychotherapy, University Duisburg-Essen, Germany; Martin Dichgans, Institute for Stroke and Dementia Research and Department of Neurology, Klinikum der Universität München, Munich, Germany; Lutz Frölich, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany; Harald Hampel, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University, Frankfurt, Germany; Michael Hüll, Centre for Geriatric Medicine and Section of Gerontopsychiatry and Neuropsychology, Medical School, University of Freiburg, Germany; Dan Rujescu, Alzheimer Memorial Center and Geriatric Psychiatry Branch, Department of Psychiatry, Ludwig-Maximilian University, Munich, Germany; Alison Goate, Carlos Cruchaga, Petra Nowotny, John C. Morris, and Kevin Mayo, Departments of Psychiatry, Neurology, and Genetics, Washington University School of Medicine, St Louis, Missouri; John S. K. Kauwe, Department of Biology, Brigham Young University, Provo, Utah; Gill Livingston, Nicholas J. Bass, Hugh Gurling, and Andrew McQuillin, Department of Mental Health Sciences, UCL, London, England; Rhian Gwilliam and Panagiotis Deloukas, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, England; and Markus M. Nöthen, Department of Genomics, Life and Brain Center, University of Bonn, Germany.
Additional Contributions: We thank the patients who participated and the physicians who helped in recruitment. This study makes use of data generated by the Wellcome Trust Case-Control Consortium. A full list of the investigators who contributed to the generation of the data is available at www.wtccc.org.uk. We acknowledge use of genotype data from the 610 group, part of the GERAD1 consortium, who were supported by funding from the Wellcome Trust (including grant GR082604MA), the Medical Research Council (including grant G0300429), the Alzheimer’s Research Trust, the Welsh Assembly Government, the Alzheimer’s Society, Ulster Garden Villages, the Northern Ireland Research and Development Office, the Royal College of Physicians/Dunhill Medical Trust, Mercer’s Institute for Research on Ageing, Bristol Research into Alzheimer’s and Care of the Elderly, the Charles Wolfson Charitable Trust, the National Institutes of Health (including grants PO1-AG026276, PO1-AG03991, RO1-AG16208, and P50-AG05681), the National Institute on Aging, the Foundation for Barnes-Jewish Hospital, the Charles and Joanne Knight Alzheimer’s Research Initiative of the Washington University Alzheimer’s Disease Research Centre, the University College Hospital/UCL Biomedical Centre, Lundbeck SA, the German Federal Ministry of Education and Research (Kompetenznetz Demenzen [grant 01GI0420], Bundesministerium für Bildung und Forschung, and Competence Network Dementia Förderkennzeichen [grants 01GI0102 and 01GI0711]), and we thank the Eli Lilly company for their financial support (to Dr Williams). We also thank the Hersenstichting Nederland (www.hersenstichting.nl), the Neuroscience Campus Amsterdam, and the section of medical genomics, the Prinses Beatrix Fonds (https://prinsesbeatrixfonds.nl), for sponsoring this work.