Letter | Published:

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

Nature Genetics volume 45, pages 14521458 (2013) | Download Citation

Abstract

Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10−8) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.

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Acknowledgements

This work was made possible by the generous participation of the control subjects, the patients and their families. iSelect chips were funded by the French National Foundation on Alzheimer's Disease and Related Disorders. Data management involved the Centre National de Génotypage and was supported by the Institut Pasteur de Lille, INSERM, FRC (Fondation pour la Recherche sur le Cerveau) and Rotary. This work has been developed and supported by the LABEX (Laboratory of Excellence Program Investment for the Future) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary Approach to Alzheimer's Disease). The French National Foundation on Alzheimer's Disease and Related Disorders and the Alzheimer's Association (Chicago, Illinois) grant supported in-person meetings and communication for IGAP, and the Alzheimer's Association (Chicago, Illinois) grant provided some funds to each consortium for analyses.

GERAD was supported by the Wellcome Trust, the MRC, Alzheimer's Research UK (ARUK) and the Welsh government. ADGC and CHARGE were supported by the US National Institutes of Health, National Institute on Aging (NIH-NIA), including grants U01 AG032984 and R01 AG033193 (additional US National Institutes of Health grant numbers are listed in the Supplementary Note). CHARGE was also supported by Erasmus Medical Center and Erasmus University.

Complete acknowledgments are detailed in the Supplementary Note.

Author information

Author notes

    • Jean-Charles Lambert
    • , Carla A Ibrahim-Verbaas
    • , Denise Harold
    • , Adam C Naj
    • , Sudha Seshadri
    • , Julie Williams
    • , Gerard D Schellenberg
    •  & Philippe Amouyel

    These authors contributed equally to this work.

    • Sudha Seshadri
    • , Julie Williams
    • , Gerard D Schellenberg
    •  & Philippe Amouyel

    These authors jointly directed this work.

Affiliations

  1. INSERM, U744, Lille, France.

    • Jean-Charles Lambert
    • , Céline Bellenguez
    • , Benjamin Grenier-Boley
    • , Vincent Chouraki
    • , Nathalie Fiévet
    •  & Philippe Amouyel
  2. Université Lille 2, Lille, France.

    • Jean-Charles Lambert
    • , Céline Bellenguez
    • , Benjamin Grenier-Boley
    • , Vincent Chouraki
    • , Florence Pasquier
    • , Vincent Deramecourt
    •  & Philippe Amouyel
  3. Institut Pasteur de Lille, Lille, France.

    • Jean-Charles Lambert
    • , Céline Bellenguez
    • , Benjamin Grenier-Boley
    • , Vincent Chouraki
    • , Nathalie Fiévet
    •  & Philippe Amouyel
  4. Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.

    • Carla A Ibrahim-Verbaas
    • , M Arfan Ikram
    •  & Renee F A G de Bruijn
  5. Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.

    • Carla A Ibrahim-Verbaas
    • , M Arfan Ikram
    • , Najaf Amin
    • , Renee F A G de Bruijn
    • , Albert Hofman
    •  & Cornelia M van Duijn
  6. Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council (MRC) Centre for Neuropsychiatric Genetics & Genomics, Cardiff University, Cardiff, UK.

    • Denise Harold
    • , Rebecca Sims
    • , Nicola Jones
    • , Charlene Thomas
    • , Amy Gerrish
    • , Melanie L Dunstan
    • , Paul Hollingworth
    • , Michael J Owen
    • , Michael C O'Donovan
    • , Lesley Jones
    • , Peter A Holmans
    • , Valentina Moskvina
    •  & Julie Williams
  7. Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Adam C Naj
  8. Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Adam C Naj
  9. Department of Medicine (Biomedical Genetics), Boston University School of Public Health, Boston, Massachusetts, USA.

    • Gyungah Jun
    • , Badri N Vardarajan
    • , Clinton Baldwin
    •  & Lindsay A Farrer
  10. Department of Ophthalmology, Boston University School of Medicine, Boston, Massachusetts, USA.

    • Gyungah Jun
    •  & Lindsay A Farrer
  11. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.

    • Gyungah Jun
    • , Anita L DeStefano
    • , Seung-Hoan Choi
    • , Kathryn L Lunetta
    •  & Lindsay A Farrer
  12. Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.

    • Joshua C Bis
    • , Annette L Fitzpatrick
    • , Tamara B Harris
    •  & Bruce M Psaty
  13. John P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida, USA.

    • Gary W Beecham
    • , Brian Kunkle
    • , John R Gilbert
    • , Kara L Hamilton-Nelson
    • , Eden R Martin
    •  & Margaret A Pericak-Vance
  14. Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miami, Florida, USA.

    • Gary W Beecham
    • , John R Gilbert
    • , Eden R Martin
    •  & Margaret A Pericak-Vance
  15. Functional Genomics Center Zurich, Eidgenössische Technische Hochschule (ETH)/University of Zurich, Zurich, Switzerland.

    • Giancarlo Russo
  16. Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA.

    • Tricia A Thornton-Wells
    •  & Jonathan L Haines
  17. Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

    • Albert V Smith
    • , Vilmundur Gudnason
    •  & Palmi V Jonsson
  18. Icelandic Heart Association, Kopavogur, Iceland.

    • Albert V Smith
    • , Vilmundur Gudnason
    •  & Gudny Eiriksdottir
  19. Department of Radiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.

    • M Arfan Ikram
  20. Netherlands Consortium for Healthy Aging, Leiden, The Netherlands.

    • M Arfan Ikram
    • , Renee F A G de Bruijn
    • , Albert Hofman
    •  & Cornelia M van Duijn
  21. Centre National de Génotypage, Institut Génomique, Commissariat à l'Energie Atomique, Evry, France.

    • Diana Zelenika
    • , Marie-Thérèse Bihoreau
    •  & Mark Lathrop
  22. Fondation Jean Dausset, Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France.

    • Yoichiro Kamatani
    •  & Mark Lathrop
  23. Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

    • Chiao-Feng Lin
    • , Otto Valladares
    • , Laura B Cantwell
    • , Li-San Wang
    •  & Gerard D Schellenberg
  24. Institute for Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.

    • Helena Schmidt
  25. Memory Clinic of Fundació Alzheimer Centre Educacional (ACE). Institut Català de Neurociències Aplicades, Barcelona, Spain.

    • Agustin Ruiz
    •  & Mercè Boada
  26. Taub Institute on Alzheimer's Disease and the Aging Brain, Department of Neurology, Columbia University, New York, New York, USA.

    • Christiane Reitz
    •  & Richard Mayeux
  27. Gertrude H. Sergievsky Center, Department of Neurology, Columbia University, New York, New York, USA.

    • Christiane Reitz
    •  & Richard Mayeux
  28. Centre National de Reference pour les Malades Alzheimer Jeunes (CNR-MAJ), Centre Hospitalier Régional Universitaire de Lille, Lille, France.

    • Florence Pasquier
    • , Vincent Deramecourt
    •  & Philippe Amouyel
  29. Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.

    • Alfredo Ramirez
    •  & Wolfgang Maier
  30. Institute of Human Genetics, University of Bonn, Bonn, Germany.

    • Alfredo Ramirez
  31. University Paris Descartes, Sorbonne Paris V, Broca Hospital, Geriatrics Department, Paris, France.

    • Olivier Hanon
  32. Department of Epidemiology, University of Washington, Seattle, Washington, USA.

    • Annette L Fitzpatrick
    • , Walter A Kukull
    •  & Bruce M Psaty
  33. Department of Global Health, University of Washington, Seattle, Washington, USA.

    • Annette L Fitzpatrick
  34. Department of Neuroscience, Mount Sinai School of Medicine, New York, New York, USA.

    • Joseph D Buxbaum
  35. Department of Psychiatry, Mount Sinai School of Medicine, New York, New York, USA.

    • Joseph D Buxbaum
  36. Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, USA.

    • Joseph D Buxbaum
  37. CNR-MAJ, INSERM, U1079, Rouen University Hospital, Rouen, France.

    • Dominique Campion
    • , David Wallon
    •  & Didier Hannequin
  38. Department of Medicine, University of Washington, Seattle, Washington, USA.

    • Paul K Crane
    •  & Eric B Larson
  39. German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.

    • Tim Becker
    •  & Wolfgang Maier
  40. Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany.

    • Tim Becker
  41. Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.

    • Carlos Cruchaga
    •  & Alison M Goate
  42. Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine, St. Louis, Missouri, USA.

    • Carlos Cruchaga
    •  & Alison M Goate
  43. Ageing Group, Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University, Belfast, UK.

    • David Craig
    • , Janet A Johnston
    • , Bernadette McGuinness
    • , Stephen Todd
    •  & Peter Passmore
  44. INSERM, U1061, Faculty of Medicine, Hôpital La Colombière, Montpellier, France.

    • Claudine Berr
    •  & Karen Ritchie
  45. Departments of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

    • Oscar L Lopez
  46. 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.

    • Philip L De Jager
  47. Program in Medical and Population Genetics, Broad Institute, Boston, Massachusetts, USA.

    • Philip L De Jager
  48. Rush Institute for Healthy Aging, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA.

    • Denis Evans
  49. Institute of Psychiatry, King's College London, Denmark Hill, London, UK.

    • Simon Lovestone
    • , Petroula Proitsi
    •  & John F Powell
  50. INSERM, U897, Victor Segalen University, Bordeaux, France.

    • Luc Letenneur
    • , Pascale Barberger-Gateau
    • , Carole Dufouil
    •  & Jean-François Dartigues
  51. Departamento de Genómica Estructural, Neocodex, Seville, Spain.

    • Francisco J Morón
  52. Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.

    • David C Rubinsztein
    •  & Peter St George-Hyslop
  53. Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.

    • Kristel Sleegers
    • , Karolien Bettens
    •  & Christine Van Broeckhoven
  54. Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.

    • Kristel Sleegers
    • , Karolien Bettens
    •  & Christine Van Broeckhoven
  55. Neurogenomics Division, Translational Genomics Research Institute, Phoenix, Arizona, USA.

    • Matthew J Huentelman
  56. Mercer's Institute for Research on Aging, St. James Hospital and Trinity College, Dublin, Ireland.

    • Michael Gill
  57. Institute of Genetics, Queen's Medical Centre, University of Nottingham, Nottingham, UK.

    • Kristelle Brown
    •  & Kevin Morgan
  58. Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

    • M Ilyas Kamboh
  59. Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

    • M Ilyas Kamboh
  60. Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden.

    • Lina Keller
    •  & Laura Fratiglioni
  61. Group Health Research Institute, Group Health, Seattle, Washington, USA.

    • Eric B Larson
    •  & Bruce M Psaty
  62. 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.

    • Robert Green
  63. Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, Florida, USA.

    • Amanda J Myers
  64. University of Bristol Institute of Clinical Neurosciences, School of Clinical Sciences, Frenchay Hospital, Bristol, UK.

    • Seth Love
  65. Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, Ontario, Canada.

    • Ekaterina Rogaeva
    •  & Peter St George-Hyslop
  66. Institute of Primary Care and Public Health, Cardiff University, Neuadd Meirionnydd, University Hospital of Wales, Heath Park, Cardiff, UK.

    • John Gallacher
    •  & Anthony Bayer
  67. Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

    • Peter St George-Hyslop
  68. Neurology Department. Biomedical Research Institute Sant Pau (IIB Sant Pau). Sant Pau Hospital. Universitat Autònoma de Barcelona, Barcelona, Spain.

    • Jordi Clarimon
    •  & Alberto Lleo
  69. Center for Networker Biomedical Research in Neurodegenerative Diseases (CIBERNED), Barcelona, Spain.

    • Jordi Clarimon
    •  & Alberto Lleo
  70. Geriatric Research, Education and Clinical Center (GRECC), Veteran Administration Puget Sound Health Care System (VAPSHCS), Seattle, Washington, USA.

    • Debby W Tsuang
  71. Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.

    • Lei Yu
    •  & David A Bennett
  72. Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece.

    • Magda Tsolaki
  73. Clinical and Behavioral Neurology, Fondazione Santa Lucia, Rome, Italy.

    • Paola Bossù
    •  & Gianfranco Spalletta
  74. MRC Prion Unit, Department of Neurodegenerative Disease, University College London Institute of Neurology, London, UK.

    • John Collinge
    •  & Simon Mead
  75. NEUROFARBA (Department of Neuroscience, Psychology, Drug Research and Child Health), University of Florence, Florence, Italy.

    • Sandro Sorbi
    •  & Benedetta Nacmias
  76. Centro di Ricerca, Trasferimento e Alta Formazione DENOTHE, University of Florence, Florence, Italy.

    • Sandro Sorbi
    •  & Benedetta Nacmias
  77. Department of Immunology, Hospital Universitario Dr. Negrin, Las Palmas de Gran Canaria, Spain.

    • Florentino Sanchez-Garcia
    •  & Maria Candida Deniz Naranjo
  78. Dementia Research Centre, Department of Neurodegenerative Disease, University College London Institute of Neurology, London, UK.

    • Nick C Fox
  79. Department of Molecular Neuroscience, Institute of Neurology, London, UK.

    • John Hardy
  80. Reta Lilla Weston Laboratories, Institute of Neurology, London, UK.

    • John Hardy
  81. Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Associazione Oasi Maria Santissima Srl, Troina, Italy.

    • Paolo Bosco
  82. Oxford Healthy Aging Project (OHAP), Clinical Trial Service Unit, University of Oxford, Oxford, UK.

    • Robert Clarke
  83. Institute of Public Health, University of Cambridge, Cambridge, UK.

    • Carol Brayne
  84. University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Milan, Italy.

    • Daniela Galimberti
  85. Neurological Clinic, University of Pisa, Pisa, Italy.

    • Michelangelo Mancuso
  86. MRC Biostatistics Unit, Cambridge, UK.

    • Fiona Matthews
  87. Urban Epidemiology, Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.

    • Susanne Moebus
  88. Section of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.

    • Patrizia Mecocci
  89. Section of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.

    • Maria Del Zompo
  90. Department of Psychiatry, University of Frankfurt, Frankfurt am Main, Germany.

    • Harald Hampel
  91. Department of Psychiatry, Ludwig Maximilians University, Munich, Germany.

    • Harald Hampel
  92. Gerontology and Geriatrics Research Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.

    • Alberto Pilotto
  93. Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas–Universidad Autónoma de Madrid, Madrid, Spain.

    • Maria Bullido
  94. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.

    • Maria Bullido
  95. Instituto de Investigación Sanitaria Hospital la Paz (IdIPaz), Madrid, Spain.

    • Maria Bullido
  96. Departement of Geriatrics, Center for Aging Brain, University of Bari, Bari, Italy.

    • Francesco Panza
  97. Department of Neuroscience, University of Parma, Parma, Italy.

    • Paolo Caffarra
  98. Center for Cognitive Disorders, Azienda Unita Sanitaria Local (AUSL), Parma, Italy.

    • Paolo Caffarra
  99. Department of Psychiatry, Saarland University Hospital, Homburg, Germany.

    • Manuel Mayhaus
    • , Sabrina Pichler
    • , Wei Gu
    •  & Matthias Riemenschneider
  100. Department of Public Health/Geriatrics, Uppsala University, Uppsala, Sweden.

    • Lars Lannfelt
    •  & Martin Ingelsson
  101. Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

    • Hakon Hakonarson
  102. Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.

    • Minerva M Carrasquillo
    • , Fanggeng Zou
    •  & Steven G Younkin
  103. National Alzheimer's Coordinating Center, University of Washington, Seattle, Washington, USA.

    • Duane Beekly
  104. Genetica Molecular, Hospital Universitario Central Asturias, Oviedo, Spain.

    • Victoria Alvarez
    •  & Eliecer Coto
  105. Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra School of Medicine, Pamplona, Spain.

    • Cristina Razquin
    •  & Pau Pastor
  106. CIBERNED, Instituto de Salud Carlos III, Madrid, Spain.

    • Pau Pastor
  107. Neurology Service, Marqués de Valdecilla University Hospital, University of Cantabria and Instituto de Formación e Investigación Marqués de Valdecilla (IFIMAV), Santander, Spain.

    • Ignacio Mateo
    •  & Onofre Combarros
  108. CIBERNED, Marqués de Valdecilla University Hospital, University of Cantabria and IFIMAV, Santander, Spain.

    • Ignacio Mateo
    •  & Onofre Combarros
  109. Department of Medical and Molecular Genetics, Indiana University, Indianapolis, Indiana, USA.

    • Kelley M Faber
    •  & Tatiana M Foroud
  110. Geriatric Department, Landspitali University Hospital, Reykjavik, Iceland.

    • Palmi V Jonsson
  111. Institute of Clinical Medicine–Neurology, University of Eastern Finland, Kuopio, Finland.

    • Hilkka Soininen
    •  & Mikko Hiltunen
  112. Department of Neurology, Kuopio University Hospital, Kuopio, Finland.

    • Hilkka Soininen
    •  & Mikko Hiltunen
  113. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.

    • Deborah Blacker
  114. Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA.

    • Deborah Blacker
  115. Department of Medicine (Geriatrics), University of Mississippi Medical Center, Jackson, Mississippi, USA.

    • Thomas H Mosley Jr
  116. Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.

    • David A Bennett
    •  & Caroline Graff
  117. Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.

    • Laura Fratiglioni
  118. Division of Clinical Neurosciences, School of Medicine, University of Southampton, Southampton, UK.

    • Clive Holmes
  119. Department of Pathology, University of Washington, Seattle, Washington, USA.

    • Thomas J Montine
  120. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

    • Jerome I Rotter
  121. 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.

    • Alexis Brice
  122. Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpital de la Pitié–Salpêtrière, Paris, France.

    • Alexis Brice
  123. Laboratory of Neurogenetics, Intramural Research Program, National Institute on Aging, Bethesda, Maryland, USA.

    • Michael A Nalls
  124. Faculty of Medicine, Imperial College, St. Mary's Hospital, London, UK.

    • Karen Ritchie
  125. Department of Biology, Brigham Young University, Provo, Utah, USA.

    • John S K Kauwe
  126. Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.

    • Eric Boerwinkle
  127. Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, USA.

    • Eric Boerwinkle
  128. Division of Epidemiology, University of Texas Health Sciences Center at Houston, Houston, Texas, USA.

    • Eric Boerwinkle
  129. Hospital Universitari Vall d'Hebron–Institut de Recerca, Universitat Autònoma de Barcelona. (VHIR-UAB), Barcelona, Spain.

    • Mercè Boada
  130. Department of Neurology, Medical University of Graz, Graz, Austria.

    • Reinhold Schmidt
  131. Department of Psychiatry, University of Halle, Halle, Germany.

    • Dan Rujescu
  132. Centre de Mémoire de Ressources et de Recherche de Bordeaux, Centre Hospitalier Universitaire (CHU) de Bordeaux, Bordeaux, France.

    • Jean-François Dartigues
  133. INSERM, U708, Victor Segalen University, Bordeaux, France.

    • Christophe Tzourio
  134. Institute of Human Genetics, Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.

    • Markus M Nöthen
  135. Department of Neurobiology, Karolinska Institutet, Care Sciences and Society, Karolinska Institute–Alzheimer's Disease Research Center (KIADRC), Stockholm, Sweden.

    • Caroline Graff
  136. Department of Health Service, University of Washington, Seattle, Washington, USA.

    • Bruce M Psaty
  137. Vanderbilt Center for Human Genetics Research, Vanderbilt University, Nashville, Tennessee, USA.

    • Jonathan L Haines
  138. McGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada.

    • Mark Lathrop
  139. Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, Bethesda, Maryland, USA.

    • Lenore J Launer
  140. Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA.

    • Lindsay A Farrer
  141. Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA.

    • Lindsay A Farrer
    •  & Sudha Seshadri
  142. Center for Medical Systems Biology, Leiden, The Netherlands.

    • Cornelia M van Duijn
  143. Centre Hospitalier Régional Universitaire de Lille, Lille, France.

    • Philippe Amouyel

Consortia

  1. European Alzheimer's Disease Initiative (EADI)

    Full lists of members and affiliations appear in the Supplementary Note

  2. Genetic and Environmental Risk in Alzheimer's Disease (GERAD)

    Full lists of members and affiliations appear in the Supplementary Note

  3. Alzheimer's Disease Genetic Consortium (ADGC)

    Full lists of members and affiliations appear in the Supplementary Note

  4. Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)

    Full lists of members and affiliations appear in the Supplementary Note

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Contributions

Study concept and design: J.-C.L., C.A.I.-V., D. Harold, A.C.N., A.L.D., J.C.B., A.V.S., M.A.I., H. Schmidt, A.L.F., V.G., O.L.L., D.W.T., D. Blacker, T.H.M., T.B.H., J.I.R., W.A.K., M. Boada, R. Schmidt, R.M., A.H., B.M.P., J.L.H., P.A.H., M.L., M.A.P.-V., L.J.L., L.A.F., C.M.v.D., V.M., S. Seshadri, J.W., G.D.S. and P.A. Acquisition of data: J.-C.L., C.A.I.-V., D. Harold, C. Bellenguez, R. Sims, G.J., B.G.-B., G.R., N.J., V.C., C. Thomas, D.Z., Y.K., A.G., H. Schmidt, M.L.D., M.-T.B., S.-H.C., P.H., V.G., C. Baldwin, C.C., C. Berr, O.L.L., P.L.D.J., D.E., L. Letenneur, G.E., K.S., A.M.G., N.F., M.J.H., M.I.K., E.B.L., A.J.M., C.D., S.T., S. Love, E.R., P.S.G.-H., L.Y., M.M.C., D. Beekly, F.Z., O.V., S.G.Y., W.G., M.J.O., K.M.F., P.V.J., M.C.O., L.B.C., D.A.B., T.B.H., R.F.A.G.d.B., T.J.M., J.I.R., K.M., T.M.F., W.A.K., J.F.P., M.A.N., K.R., J.S.K.K., E.B., M.R., M. Boada, L.-S.W., J.-F.D., C. Tzourio, M.M.N., B.M.P., L.J., J.L.H., M.L., L.J.L., L.A.F., A.H., C.M.v.D., S. Seshadri, J.W., G.D.S. and P.A. Sample contribution: A. Ruiz, F. Pasquier, A. Ramirez, O.H., J.D.B., D. Campion, P.K.C., C. Baldwin, T.B., C.C., D. Craig, V.D., J.A.J., S. Lovestone, F.J.M., D.C.R., K.S., A.M.G., N.F., M.G., K. Brown, M.I.K., L.K., P.B.-G., B.M., R.G., A.J.M., D.W., E.R., J.G., P.S.G.-H., J.C., A.L., A. Bayer, M.T., P. Bossù, G.S., P. Proitsi, J.C., S. Sorbi, F.S.-G., N.C.F., J.H., M.C.D.N., P. Bosco, R.C., C. Brayne, D.G., M. Mancuso, F.M., S. Moebus, P.M., M.D.Z., W.M., H. Hampel, A.P., M. Bullido, F. Panza, P.C., B.N., M. Mayhaus, L. Lannfelt, H. Hakonarson, S.P., M.M.C., M.I., V.A., S.G.Y., E.C., C. Razquin, P. Pastor, I.M., O.C., H. Soininen, S. Mead, D.A.B., L.F., C.H., P. Passmore, T.J.M., K. Bettens, A. Brice, D. Hannequin, K.R., M.R., M.H., D.R., C.G. and C.V.B. Data analysis: C.A.I.-V., D. Harold, A.C.N., R. Sims, C. Bellenguez, G.J., A.L.D., J.C.B., G.W.B., B.G.-B., G.R., T.A.T.-W., N.J., A.V.S., V.C., M.A.I., D.Z., Y.K., B.N.V., C.-F.L., A.G., B.K., C. Reitz, J.R.G., O.V., W.A.K., K.L.L., K.L.H.-N., E.R.M., L.-S.W., B.M.P., M.L., V.M. and J.W. Statistical analysis and interpretation: J.-C.L., C.A.I.-V., D. Harold, A.C.N., C. Bellenguez, G.J., A.L.D., J.C.B., G.W.B., T.A.T.-W., A.V.S., V.C., M.A.I., B.N.V., Y.K., C.-F.L., B.K., C. Reitz, A.L.F., N.A., J.R.G., R.F.A.G.d.B., W.A.K., K.L.L., E.R.M., L.-S.W., B.M.P., L.J., J.L.H., P.A.H., M.A.P.-V., L.J.L., L.A.F., C.M.v.D., V.M., S. Seshadri, J.W., G.D.S. and P.A. Drafting of the manuscript: J.-C.L., C.A.I.-V., D. Harold, A.C.N., C. Bellenguez, A.L.D., J.C.B., A.V.S., R.M., B.M.P., J.L.H., M.A.P.-V., L.J.L., L.A.F., C.M.v.D., C.V.B., S. Seshadri, J.W., G.D.S. and P.A.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Julie Williams or Philippe Amouyel.

Supplementary information

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    Supplementary Text and Figures

    Supplementary Figures 1–18, Supplementary Tables 1–10 and Supplementary Note

About this article

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DOI

https://doi.org/10.1038/ng.2802

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