Nat Genet · 2013

Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease

Lambert JC, Ibrahim-Verbaas CA, Harold D, Naj AC, Sims R, Bellenguez C, DeStafano AL, Bis JC, Beecham GW, Grenier-Boley B, Russo G, Thorton-Wells TA, Jones N, Smith AV, Chouraki V, Thomas C, Ikram MA, Zelenika D, Vardarajan BN, Kamatani Y, Lin CF, Gerrish A, Gerrish A, Schmidt H, Kunkle B, Dunstan ML, Ruiz A, Bihoreau MT, Choi SH, Reitz C, Pasquier F, Cruchaga C, Craig D, Amin N, Berr C, Lopez OL, De Jager PL, Deramecourt V, Johnston JA, Evans D, Lovestone S, Letenneur L, Morón FJ, Rubinsztein DC, Eiriksdottir G, Sleegers K, Goate AM, Fiévet N, Huentelman MW, Gill M, Brown K, Kamboh MI, Keller L, Barberger-Gateau P, McGuiness B, Larson EB, Green R, Myers AJ, Dufouil C, Todd S, Wallon D, Love S, Rogaeva E, Gallacher J, St George-Hyslop P, Clarimon J, Lleo A, Bayer A, Tsuang DW, Yu L, Tsolaki M, Bossù P, Spalletta G, Proitsi P, Collinge J, Sorbi S, Sanchez-Garcia F, Fox NC, Hardy J, Deniz Naranjo MC, Bosco P, Clarke R, Brayne C, Galimberti D, Mancuso M, Matthews F, European Alzheimer's Disease Initiative (EADI), Genetic and Environmental Risk in Alzheimer's Disease, Alzheimer's Disease Genetic Consortium, Cohorts for Heart and Aging Research in Genomic Epidemiology, Moebus S, Mecocci P, Del Zompo M, Maier W, Hampel H, Pilotto A, Bullido M, Panza F, Caffarra P, Nacmias B, Gilbert JR, Mayhaus M, Lannefelt L, Hakonarson H, Pichler S, Carrasquillo MM, Ingelsson M, Beekly D, Alvarez V, Zou F, Valladares O, Younkin SG, Coto E, Hamilton-Nelson KL, Gu W, Razquin C, Pastor P, Mateo I, Owen MJ, Faber KM, Jonsson PV, Combarros O, O'Donovan MC, Cantwell LB, Soininen H, Blacker D, Mead S, Mosley TH, Bennett DA, Harris TB, Fratiglioni L, Holmes C, de Bruijn RF, Passmore P, Montine TJ, Bettens K, Rotter JI, Brice A, Morgan K, Foroud TM, Kukull WA, Hannequin D, Powell JF, Nalls MA, Ritchie K, Lunetta KL, Kauwe JS, Boerwinkle E, Riemenschneider M, Boada M, Hiltuenen M, Martin ER, Schmidt R, Rujescu D, Wang LS, Dartigues JF, Mayeux R, Tzourio C, Hofman A, Nöthen MM, Graff C, Psaty BM, Jones L, Haines JL, Holmans PA, Lathrop M, Pericak-Vance MA, Launer LJ, Farrer LA, van Duijn CM, Van Broeckhoven C, Moskvina V, Seshadri S, Williams J, Schellenberg GD, Amouyel P.

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Lambert JC — INSERM, U744, Lille, France.
Ibrahim-Verbaas CA — Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Harold D — Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council (MRC) Centre for Neuropsychiatric Genetics & Genomics, Cardiff University, Cardiff, UK.
Naj AC — Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Sims R — Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council (MRC) Centre for Neuropsychiatric Genetics & Genomics, Cardiff University, Cardiff, UK.
Bellenguez C — INSERM, U744, Lille, France.
DeStafano AL — Department of Medicine (Biomedical Genetics), Boston University School of Public Health, Boston, Massachusetts, USA.
Bis JC — Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
Beecham GW — Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.
Grenier-Boley B — John P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida, USA.
Russo G — INSERM, U744, Lille, France.
Thorton-Wells TA — Functional Genomics Center Zurich, Eidgenössische Technische Hochschule (ETH)/University of Zurich, Zurich, Switzerland.
Jones N — Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA.
Smith AV — Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council (MRC) Centre for Neuropsychiatric Genetics & Genomics, Cardiff University, Cardiff, UK.
Chouraki V — Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Thomas C — INSERM, U744, Lille, France.
Ikram MA — Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council (MRC) Centre for Neuropsychiatric Genetics & Genomics, Cardiff University, Cardiff, UK.
Zelenika D — Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Vardarajan BN — Centre National de Génotypage, Institut Génomique, Commissariat à l’Energie Atomique, Evry, France.
Kamatani Y — Department of Medicine (Biomedical Genetics), Boston University School of Public Health, Boston, Massachusetts, USA.
Lin CF — Fondation Jean Dausset, Centre d’Etude du Polymorphisme Humain (CEPH), Paris, France.
Gerrish A — Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Gerrish A — Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Schmidt H — Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council (MRC) Centre for Neuropsychiatric Genetics & Genomics, Cardiff University, Cardiff, UK.
Kunkle B — Institute for Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.
Dunstan ML — John P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida, USA.
Ruiz A — Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council (MRC) Centre for Neuropsychiatric Genetics & Genomics, Cardiff University, Cardiff, UK.
Bihoreau MT — Memory Clinic of Fundació Alzheimer Centre Educacional (ACE). Institut Català de Neurociències Aplicades, Barcelona, Spain.
Choi SH — Centre National de Génotypage, Institut Génomique, Commissariat à l’Energie Atomique, Evry, France.
Reitz C — Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
Pasquier F — Taub Institute on Alzheimer’s Disease and the Aging Brain, Department of Neurology, Columbia University, New York, New York, USA.
Cruchaga C — Université Lille 2, Lille, France.
Craig D — Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council (MRC) Centre for Neuropsychiatric Genetics & Genomics, Cardiff University, Cardiff, UK.
Amin N — Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
Berr C — University Paris Descartes, Sorbonne Paris V, Broca Hospital, Geriatrics Department, Paris, France.
Lopez OL — Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.
De Jager PL — Department of Neuroscience, Mount Sinai School of Medicine, New York, New York, USA.
Deramecourt V — CNR-MAJ, INSERM, U1079, Rouen University Hospital, Rouen, France.
Johnston JA — Department of Medicine, University of Washington, Seattle, Washington, USA.
Evans D — Department of Medicine (Biomedical Genetics), Boston University School of Public Health, Boston, Massachusetts, USA.
Lovestone S — German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Letenneur L — Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Morón FJ — Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
Rubinsztein DC — Ageing Group, Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University, Belfast, UK.
Eiriksdottir G — Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Sleegers K — INSERM, U1061, Faculty of Medicine, Hôpital La Colombière, Montpellier, France.
Goate AM — Departments of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Fiévet N — Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Department of Neurology & Psychiatry, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Huentelman MW — Université Lille 2, Lille, France.
Gill M — Ageing Group, Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University, Belfast, UK.
Brown K — Rush Institute for Healthy Aging, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA.
Kamboh MI — Institute of Psychiatry, King’s College London, Denmark Hill, London, UK.
Keller L — INSERM, U897, Victor Segalen University, Bordeaux, France.
Barberger-Gateau P — Departamento de Genómica Estructural, Neocodex, Seville, Spain.
McGuiness B — Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
Larson EB — Icelandic Heart Association, Kopavogur, Iceland.
Green R — Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.
Myers AJ — Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
Dufouil C — INSERM, U744, Lille, France.
Todd S — Neurogenomics Division, Translational Genomics Research Institute, Phoenix, Arizona, USA.
Wallon D — Mercer’s Institute for Research on Aging, St. James Hospital and Trinity College, Dublin, Ireland.
Love S — Institute of Genetics, Queen’s Medical Centre, University of Nottingham, Nottingham, UK.
Rogaeva E — Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Gallacher J — Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
St George-Hyslop P — INSERM, U897, Victor Segalen University, Bordeaux, France.
Clarimon J — Ageing Group, Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University, Belfast, UK.
Lleo A — Department of Medicine, University of Washington, Seattle, Washington, USA.
Bayer A — Department of Medicine and Partners Center for Personalized Genetic Medicine, Division of Genetics, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Tsuang DW — Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, Florida, USA.
Yu L — INSERM, U897, Victor Segalen University, Bordeaux, France.
Tsolaki M — Ageing Group, Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University, Belfast, UK.
Bossù P — CNR-MAJ, INSERM, U1079, Rouen University Hospital, Rouen, France.
Spalletta G — University of Bristol Institute of Clinical Neurosciences, School of Clinical Sciences, Frenchay Hospital, Bristol, UK.
Proitsi P — Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, Ontario, Canada.
Collinge J — Institute of Primary Care and Public Health, Cardiff University, Neuadd Meirionnydd, University Hospital of Wales, Heath Park, Cardiff, UK.
Sorbi S — Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
Sanchez-Garcia F — Neurology Department. Biomedical Research Institute Sant Pau (IIB Sant Pau). Sant Pau Hospital. Universitat Autònoma de Barcelona, Barcelona, Spain.
Fox NC — Neurology Department. Biomedical Research Institute Sant Pau (IIB Sant Pau). Sant Pau Hospital. Universitat Autònoma de Barcelona, Barcelona, Spain.
Hardy J — Institute of Primary Care and Public Health, Cardiff University, Neuadd Meirionnydd, University Hospital of Wales, Heath Park, Cardiff, UK.
Deniz Naranjo MC — Geriatric Research, Education and Clinical Center (GRECC), Veteran Administration Puget Sound Health Care System (VAPSHCS), Seattle, Washington, USA.
Bosco P — Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.
Clarke R — Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Brayne C — Clinical and Behavioral Neurology, Fondazione Santa Lucia, Rome, Italy.
Galimberti D — Clinical and Behavioral Neurology, Fondazione Santa Lucia, Rome, Italy.
Mancuso M — Institute of Psychiatry, King’s College London, Denmark Hill, London, UK.
Matthews F — MRC Prion Unit, Department of Neurodegenerative Disease, University College London Institute of Neurology, London, UK.
— — NEUROFARBA (Department of Neuroscience, Psychology, Drug Research and Child Health), University of Florence, Florence, Italy.
— — Department of Immunology, Hospital Universitario Dr. Negrin, Las Palmas de Gran Canaria, Spain.
— — Dementia Research Centre, Department of Neurodegenerative Disease, University College London Institute of Neurology, London, UK.
— — Department of Molecular Neuroscience, Institute of Neurology, London, UK.
Moebus S — Department of Immunology, Hospital Universitario Dr. Negrin, Las Palmas de Gran Canaria, Spain.
Mecocci P — Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Associazione Oasi Maria Santissima Srl, Troina, Italy.
Del Zompo M — Oxford Healthy Aging Project (OHAP), Clinical Trial Service Unit, University of Oxford, Oxford, UK.
Maier W — Institute of Public Health, University of Cambridge, Cambridge, UK.
Hampel H — University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Milan, Italy.
Pilotto A — Neurological Clinic, University of Pisa, Pisa, Italy.
Bullido M — MRC Biostatistics Unit, Cambridge, UK.
Mayhaus M — Urban Epidemiology, Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Lannefelt L — Section of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.
Hakonarson H — Section of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
Pichler S — Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
Carrasquillo MM — Department of Psychiatry, University of Frankfurt, Frankfurt am Main, Germany.
Ingelsson M — Gerontology and Geriatrics Research Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
Beekly D — Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas–Universidad Autónoma de Madrid, Madrid, Spain.
Alvarez V — Departement of Geriatrics, Center for Aging Brain, University of Bari, Bari, Italy.
Zou F — Department of Neuroscience, University of Parma, Parma, Italy.
Valladares O — NEUROFARBA (Department of Neuroscience, Psychology, Drug Research and Child Health), University of Florence, Florence, Italy.
Younkin SG — John P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida, USA.
Coto E — Department of Psychiatry, Saarland University Hospital, Homburg, Germany.
Hamilton-Nelson KL — Department of Public Health/Geriatrics, Uppsala University, Uppsala, Sweden.
Gu W — Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Razquin C — Department of Psychiatry, Saarland University Hospital, Homburg, Germany.
Pastor P — Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Mateo I — Department of Public Health/Geriatrics, Uppsala University, Uppsala, Sweden.
Owen MJ — National Alzheimer’s Coordinating Center, University of Washington, Seattle, Washington, USA.
Faber KM — Genetica Molecular, Hospital Universitario Central Asturias, Oviedo, Spain.
Jonsson PV — Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Combarros O — Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
O'Donovan MC — Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Cantwell LB — Genetica Molecular, Hospital Universitario Central Asturias, Oviedo, Spain.
Soininen H — John P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida, USA.
Blacker D — Department of Psychiatry, Saarland University Hospital, Homburg, Germany.
Mead S — Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra School of Medicine, Pamplona, Spain.
Mosley TH Jr — Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra School of Medicine, Pamplona, Spain.
Bennett DA — Neurology Service, Marqués de Valdecilla University Hospital, University of Cantabria and Instituto de Formación e Investigación Marqués de Valdecilla (IFIMAV), Santander, Spain.
Harris TB — Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council (MRC) Centre for Neuropsychiatric Genetics & Genomics, Cardiff University, Cardiff, UK.
Fratiglioni L — Department of Medical and Molecular Genetics, Indiana University, Indianapolis, Indiana, USA.
Holmes C — Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
de Bruijn RF — Neurology Service, Marqués de Valdecilla University Hospital, University of Cantabria and Instituto de Formación e Investigación Marqués de Valdecilla (IFIMAV), Santander, Spain.
Passmore P — Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council (MRC) Centre for Neuropsychiatric Genetics & Genomics, Cardiff University, Cardiff, UK.
Montine TJ — Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Bettens K — Institute of Clinical Medicine–Neurology, University of Eastern Finland, Kuopio, Finland.
Rotter JI — Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
Brice A — MRC Prion Unit, Department of Neurodegenerative Disease, University College London Institute of Neurology, London, UK.
Morgan K — Department of Medicine (Geriatrics), University of Mississippi Medical Center, Jackson, Mississippi, USA.
Foroud TM — Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.
Kukull WA — Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.
Hannequin D — Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
Powell JF — Division of Clinical Neurosciences, School of Medicine, University of Southampton, Southampton, UK.
Nalls MA — Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Ritchie K — Ageing Group, Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University, Belfast, UK.
Lunetta KL — Department of Pathology, University of Washington, Seattle, Washington, USA.
Kauwe JS — Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.
Boerwinkle E — Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Riemenschneider M — INSERM UMRS 975, CNRS UMR 7225, Université Pierre et Marie Curie, Centre de Recherche de l’Institut du Cerveau et de la Moëlle Epinière (CRICM), Hôpital de la Salpêtrière, Paris, France.
Boada M — Institute of Genetics, Queen’s Medical Centre, University of Nottingham, Nottingham, UK.
Hiltuenen M — Department of Medical and Molecular Genetics, Indiana University, Indianapolis, Indiana, USA.
Martin ER — Department of Epidemiology, University of Washington, Seattle, Washington, USA.
Schmidt R — CNR-MAJ, INSERM, U1079, Rouen University Hospital, Rouen, France.
Rujescu D — Institute of Psychiatry, King’s College London, Denmark Hill, London, UK.
Wang LS — Laboratory of Neurogenetics, Intramural Research Program, National Institute on Aging, Bethesda, Maryland, USA.
Dartigues JF — INSERM, U1061, Faculty of Medicine, Hôpital La Colombière, Montpellier, France.
Mayeux R — Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
Tzourio C — Department of Biology, Brigham Young University, Provo, Utah, USA.
Hofman A — Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
Nöthen MM — Department of Psychiatry, Saarland University Hospital, Homburg, Germany.
Graff C — Memory Clinic of Fundació Alzheimer Centre Educacional (ACE). Institut Català de Neurociències Aplicades, Barcelona, Spain.
Psaty BM — Institute of Clinical Medicine–Neurology, University of Eastern Finland, Kuopio, Finland.
Jones L — John P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida, USA.
Haines JL — Department of Neurology, Medical University of Graz, Graz, Austria.
Holmans PA — Department of Psychiatry, University of Halle, Halle, Germany.
Lathrop M — Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Pericak-Vance MA — INSERM, U897, Victor Segalen University, Bordeaux, France.
Launer LJ — Taub Institute on Alzheimer’s Disease and the Aging Brain, Department of Neurology, Columbia University, New York, New York, USA.
Farrer LA — INSERM, U708, Victor Segalen University, Bordeaux, France.
van Duijn CM — Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Van Broeckhoven C — Institute of Human Genetics, Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
Moskvina V — Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
Seshadri S — Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.
Williams J — Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council (MRC) Centre for Neuropsychiatric Genetics & Genomics, Cardiff University, Cardiff, UK.
Schellenberg GD — Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA.
Amouyel P — Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council (MRC) Centre for Neuropsychiatric Genetics & Genomics, Cardiff University, Cardiff, UK.