Letter | Published:

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

Nature Genetics volume 43, pages 429435 (2011) | Download Citation

Abstract

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10−5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10−17; including ADGC data, meta P = 5.0 × 10−21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10−14; including ADGC data, meta P = 1.2 × 10−16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10−4; including ADGC data, meta P = 8.6 × 10−9), CD33 (GERAD+, P = 2.2 × 10−4; including ADGC data, meta P = 1.6 × 10−9) and EPHA1 (GERAD+, P = 3.4 × 10−4; including ADGC data, meta P = 6.0 × 10−10).

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Acknowledgements

For complete acknowledgments, please see the Supplementary Note. We thank the individuals and families who took part in this research and those who funded the groups who contributed to this study: Wellcome Trust; Medical Research Council (UK); Alzheimer's Research UK; the Welsh Assembly Government; Mercer's Institute for Research on Ageing; Alzheimer's Society; Ulster Garden Villages; Northern Ireland R&D Office; Royal College of Physicians; Dunhill Medical Trust; Bristol Research into Alzheimer's and Care of the Eldery; US National Institutes of Health, the Barnes Jewish Foundation; Charles and Joanne Knight Alzheimer's Research Initiative; University College London (UCL) Hospital/UCL Biomedical Centre; Lundbeck; German Federal Ministry of Education and Research Competence Network Dementia and Competence Network Degenerative Dementia; Alfried Krupp von Bohlen und Halbach-Stiftung; Intramural Research Program of the National Institute of Ageing Department of Health and Human Services; University of Antwerp, Fund for Scientific Research-Flanders; Foundation for Alzheimer Research; Methusalem Excellence grant; Federal Science Policy Office Interuniversity Attraction Poles program; Mayo AD Research Center; National Institute of Neurological Disorders and Stroke; Robert and Clarice Smith Postdoctoral Fellowship and AD Research Program; Palumbo Professorship in AD Research; Carl Edward and Susan Bass Bolch Gift; Institut Pasteur de Lille; Centre National de Génotypage; Fondation pour la Recherche Médicale Caisse; Nationale Maladie des Travailleurs Salariés, Direction Générale de la Sant; Institut de la Longévité; Agence Française de Sécurité Sanitaire des Produits de Santé; Aquitaine and Bourgogne Regional Councils; Fondation de France; French Ministry of Research/Institute national de la santé et de la recherché medicale; Eisai; Health Research Council of the Academy of Finland; Nordic Centre of Excellence in Neurodegeneration; Italian Ministry of Research; Carimonte Foundation; Italian Ministry of Health; Fondazione Monzino; Ministerio de Educación y Ciencia the Ministerio de Sanidad y Consumo; Fundación Ramón Areces; National Institute of Biomedical Imaging Bioengineering; Abbott; AstraZeneca, Bayer Schering Pharma; Bristol-Myers Squibb; Elan; Genentech; GE; GlaxoSmithKline; Innogenetics; Johnson and Johnson; Eli Lilly; Medpace; Merck; Novartis; Pfizer; Hoffman-La Roche; Schering-Plough; Synarc; Wyeth; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; US Food and Drug Administration; Foundation for the National Institutes of Health Northern California Institute for Research and Education; Dana Foundation; German National Genome Research Network; German Ministry for Education and Research; National Institute on Deafness and Other Communication Disorders; Hjartavernd; Althingi; National Heart Lung and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; Robert Dawson Evans Endowment; Netherlands Organisation of Scientific Research; Netherlands Genomics Initiative; Erasmus Medical Center; Netherlands organization for scientific research; Netherlands Organization for the Health Research and Development; the Research Institute for Diseases in the Elderly; Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission and the Municipality of Rotterdam. G.W. was partly funded by the NIHR Biomedical Research Centre Programme, Oxford. The Leeds sample collection was funded by the Health Foundation.

Author information

Author notes

    • Paul Hollingworth
    • , Denise Harold
    • , Rebecca Sims
    • , Amy Gerrish
    • , Jean-Charles Lambert
    •  & Minerva M Carrasquillo

    These authors contributed equally to this work.

Affiliations

  1. Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Neurosciences and Mental Health Research Institute, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK.

    • Paul Hollingworth
    • , Denise Harold
    • , Rebecca Sims
    • , Amy Gerrish
    • , Richard Abraham
    • , Marian L Hamshere
    • , Jaspreet Singh Pahwa
    • , Valentina Moskvina
    • , Kimberley Dowzell
    • , Nicola Jones
    • , Alexandra Stretton
    • , Charlene Thomas
    • , Alex Richards
    • , Dobril Ivanov
    • , Caroline Widdowson
    • , Jade Chapman
    • , Lesley Jones
    • , Peter A Holmans
    • , Michael J Owen
    • , Michael O'Donovan
    •  & Julie Williams
  2. INSERM U744, F-59019 Lille, France.

    • Jean-Charles Lambert
    • , Vincent Chouraki
    • , Benjamin Genier-Boley
    •  & Philippe Amouyel
  3. Institut Pasteur de Lille, F-59019, Lille, France.

    • Jean-Charles Lambert
    • , Vincent Chouraki
    • , Benjamin Genier-Boley
    •  & Philippe Amouyel
  4. Université de Lille Nord de France, F-59000 Lille, France.

    • Jean-Charles Lambert
    • , Vincent Chouraki
    • , Benjamin Genier-Boley
    • , Florence Pasquier
    •  & Philippe Amouyel
  5. Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida, USA.

    • Minerva M Carrasquillo
    • , Dennis W Dickson
    • , Neill R Graff-Radford
    •  & Steven G Younkin
  6. National Institute for Health Research Biomedical Research Centre for Mental Health at the South London and Maudsley National Health Service Foundation Trust and Institute of Psychiatry, Kings College, London, UK.

    • Simon Lovestone
  7. Department of Neuroscience, Institute of Psychiatry, Kings College, London, UK.

    • Simon Lovestone
    • , John Powell
    • , Petroula Proitsi
    •  & Michelle K Lupton
  8. Institute of Public Health, University of Cambridge, Cambridge, UK.

    • Carol Brayne
  9. Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.

    • David C Rubinsztein
  10. Mercer's Institute for Research on Aging, St. James Hospital and Trinity College, Dublin, Ireland.

    • Michael Gill
    • , Brian Lawlor
    •  & Aoibhinn Lynch
  11. Institute of Genetics, Queen's Medical Centre, University of Nottingham, Nottingham, UK.

    • Kristelle S Brown
    •  & Kevin Morgan
  12. Ageing Group, Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.

    • Peter A Passmore
    • , David Craig
    • , Bernadette McGuinness
    •  & Stephen Todd
  13. Division of Clinical Neurosciences, School of Medicine, University of Southampton, Southampton, UK.

    • Clive Holmes
  14. Neurodegeneration and Mental Health Research Group, School of Community Based Medicine, University of Manchester, Hope Hospital, Stott Lane, Salford, Manchester, UK.

    • David Mann
    •  & Emma R L C Vardy
  15. Oxford Project to Investigate Memory and Ageing (OPTIMA), University of Oxford, John Radcliffe Hospital, Oxford, UK.

    • A David Smith
    • , Helen Beaumont
    •  & Donald Warden
  16. Nuffield Department of Clinical Medicine, Medical Sciences Division. University of Oxford, Headington, Oxford, UK.

    • Gordon Wilcock
  17. Dementia Research Group, University of Bristol Institute of Clinical Neurosciences, Frenchay Hospital, Bristol, UK.

    • Seth Love
    •  & Patrick G Kehoe
  18. Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, LIGHT Laboratories, University of Leeds, Leeds, UK.

    • Nigel M Hooper
    •  & Emma R L C Vardy
  19. Cerebral Function Unit, Salford Royal National Health Service (NHS) Trust, Stott Lane, Salford, UK.

    • Emma R L C Vardy
  20. Department of Molecular Neuroscience, Institute of Neurology, London, UK.

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

    • John Hardy
  22. Department of Neurodegenerative Disease, University College London, Institute of Neurology, London, UK.

    • Simon Mead
    • , Nick C Fox
    • , Martin Rossor
    •  & John Collinge
  23. Department of Psychiatry, University of Bonn, Bonn, Germany.

    • Wolfgang Maier
    • , Frank Jessen
    • , Britta Schürmann
    • , Reiner Heun
    •  & Heike Kölsch
  24. German Centre for Neurodegenerative Diseases, Bonn, Bonn, Germany.

    • Wolfgang Maier
    •  & Eckart Rüther
  25. Institute for Molecular Psychiatry, University of Bonn, Bonn, Germany.

    • Eckart Rüther
    •  & Markus M Nöthen
  26. Department of Psychiatry, University of Göttingen, Göttingen, Germany.

    • Eckart Rüther
    •  & Britta Schürmann
  27. Department of Psychiatry, Royal Derby Hospital, Derby, UK.

    • Reiner Heun
  28. Institute of Primary Medical Care, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

    • Hendrik van den Bussche
  29. Department of Psychiatry, Charité Berlin, Berlin, Germany.

    • Isabella Heuser
  30. Department of Psychiatry and Psychotherapy, University of Erlangen, Nuremberg, Germany.

    • Johannes Kornhuber
  31. Landschaftsverband Rheinland-Hospital Essen, Department of Psychiatry and Psychotherapy, University Duisburg-Essen, Essen, Germany.

    • Jens Wiltfang
  32. Department of Neurology, Klinikum der Universität München, Munich, Germany.

    • Martin Dichgans
  33. Institute for Stroke and Dementia Research, Klinikum der Universität München, Munich, Germany.

    • Martin Dichgans
  34. Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.

    • Lutz Frölich
  35. Department of Psychiatry, Psychsomatic Medicine and Psychotherapy, Johann Wolfgang Goethe-University, Frankfurt, Germany.

    • Harald Hampel
  36. Department of Primary Care and Public Health, School of Medicine, Cardiff University, Cardiff, UK.

    • John Gallacher
    •  & Ina Giegling
  37. Centre for Geriatric Medicine and Section of Gerontopsychiatry and Neuropsychology, University of Freiburg, Freiburg, Germany.

    • Michael Hüll
    •  & Dan Rujescu
  38. Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri, USA.

    • Alison M Goate
    • , Carlos Cruchaga
    • , Petra Nowotny
    •  & Kevin Mayo
  39. Department of Neurology, Washington University School of Medicine, St Louis, Missouri, USA.

    • Alison M Goate
    •  & John C Morris
  40. Department of Genetics, Washington University School of Medicine, St Louis, Missouri, USA.

    • Alison M Goate
  41. Department of Biology, Brigham Young University, Provo, Utah, USA.

    • John S K Kauwe
  42. Institute Born-Bunge, University of Antwerp, Antwerpen, Belgium.

    • Kristel Sleegers
    • , Karolien Bettens
    • , Sebastiaan Engelborghs
    • , Peter P De Deyn
    •  & Christine Van Broeckhoven
  43. Neurodegenerative Brain Diseases group, Department of Molecular Genetics, Vlaams Interuniversitair Instituut voor Biotechnologie, Antwerpen, Belgium.

    • Kristel Sleegers
    • , Karolien Bettens
    •  & Christine Van Broeckhoven
  44. Memory Clinic and Department of Neurology, ZiekenhuisNetwerk Antwerpen, Middelheim, Antwerpen, Belgium.

    • Sebastiaan Engelborghs
    •  & Peter P De Deyn
  45. Department of Mental Health Sciences, University College London, London UK.

    • Gill Livingston
    • , Nicholas J Bass
    • , Hugh Gurling
    •  & Andrew McQuillin
  46. The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.

    • Rhian Gwilliam
    •  & Panagiotis Deloukas
  47. MRC Centre for Neurodegeneration Research, Department of Clinical Neuroscience, King's College London, Institute of Psychiatry, London, UK.

    • Ammar Al-Chalabi
    •  & Christopher E Shaw
  48. Third Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece.

    • Magda Tsolaki
  49. Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.

    • Andrew B Singleton
    •  & Rita Guerreiro
  50. Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.

    • Thomas W Mühleisen
    •  & Markus M Nöthen
  51. Institute of Human Genetics, University of Bonn, Bonn, Germany.

    • Thomas W Mühleisen
    •  & Markus M Nöthen
  52. Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany.

    • Susanne Moebus
    •  & Karl-Heinz Jöckel
  53. Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.

    • Norman Klopp
    •  & H-Erich Wichmann
  54. Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.

    • H-Erich Wichmann
  55. Klinikum Grosshadern, Munich, Germany.

    • H-Erich Wichmann
  56. Division of Biomedical Statistics and Informatics, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA.

    • V Shane Pankratz
  57. Department of Neurology, St. Olav's Hospital, Trondheim, Norway.

    • Sigrid B Sando
    •  & Jan O Aasly
  58. Department of Neuroscience, Norwegian University of Science and Technology, NTNU, 7491 Trondheim Norway.

    • Sigrid B Sando
    •  & Jan O Aasly
  59. Department of Neurodegenerative Disorders, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.

    • Maria Barcikowska
  60. Department of Neurology, Mayo Clinic College of Medicine, Jacksonville, Florida, USA.

    • Zbigniew K Wszolek
    •  & Neill R Graff-Radford
  61. Department of Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.

    • Ronald C Petersen
  62. Mayo Alzheimer Disease Research Center, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.

    • Ronald C Petersen
  63. Department of Epidemiology, Erasmus Medical Center, University Medical Center, Rotterdam, The Netherlands.

    • Cornelia M van Duijn
    • , Monique M B Breteler
    •  & M Arfan Ikram
  64. Netherlands Consortium for Healthy Aging, Leiden, The Netherlands.

    • Cornelia M van Duijn
    • , Monique M B Breteler
    •  & M Arfan Ikram
  65. Departments of Neurology and Biostatistics, Boston University School of Medicine, Boston, Massachusetts, USA.

    • Anita L DeStefano
  66. The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.

    • Anita L DeStefano
    •  & Sudha Seshadri
  67. Department of Epidemiology, University of Washington, Seattle, Washington, USA.

    • Annette L Fitzpatrick
  68. Department of Neurology, The Alzheimer's Disease Research Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

    • Oscar Lopez
  69. Department of Psychiatry, The Alzheimer's Disease Research Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

    • Oscar Lopez
  70. Neuroepidemiology Section, Laboratory of Epidemiology, Demography and Biometry (LJL), National Institute on Aging, Washington DC, USA.

    • Lenore J Launer
  71. Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA.

    • Sudha Seshadri
  72. INSERM U888, Hôpital La Colombière, Montpellier, France.

    • Claudine Berr
  73. INSERM U614, Faculté de Médecine-Pharmacie de Rouen, Rouen, France.

    • Dominique Campion
  74. Unité Mixte de Recherche 894, Inserm Faculté de Médecine, Université Paris Descartes, Paris, France.

    • Jacques Epelbaum
  75. INSERM U897, Victor Segalen University, Bordeaux, France.

    • Jean-François Dartigues
  76. INSERM U708, Paris, France.

    • Christophe Tzourio
    •  & Annick Alpérovitch
  77. Centre National de Genotypage, Institut Genomique, Commissariat à l'énergie Atomique, Evry, France.

    • Mark Lathrop
  78. The Foundation Jean Dausset-Centre d'Etude du Polymorphisme Humain, Paris, France.

    • Mark Lathrop
  79. Department of Psychiatry and Psychotherapy, Universitätsklinikum des Saarlandes, Universität des Saarlandes Saarbruecken Germany.

    • Thomas M Feulner
    • , Patricia Friedrich
    • , Caterina Riehle
    • , Manuel Mayhaus
    •  & Matthias Riemenschneider
  80. Institute of Medical Informatics and Statistics, Christian-Albrechts-University, Kiel, Germany.

    • Michael Krawczak
  81. Biobank Popgen, Institute of Experimental Medicine, Section of Epidemiology, Christian-Albrechts-University, Kiel, Germany.

    • Michael Krawczak
    •  & Stefan Schreiber
  82. Institute for Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany.

    • Michael Krawczak
    • , Stefan Schreiber
    •  & S Nicolhaus
  83. Institute of Medical Statistics and Epidemiology, Klinikum Rechts der Isar, Technische Universität, München, Germany.

    • Stefan Wagenpfeil
  84. deCODE Genetics, Reykjavik, Iceland.

    • Stacy Steinberg
    • , Hreinn Stefansson
    •  & Thorlakur Jonsson
  85. deCODE Genetics and University of Iceland, Faculty of Medicine, Reykjavik, Iceland.

    • Kari Stefansson
  86. Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

    • Jon Snædal
    • , Sigurbjörn Björnsson
    •  & Palmi V Jonsson
  87. Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.

    • Mikko Hiltunen
    •  & Hilkka Soininen
  88. Neurology Service, 'Marqués de Valdecilla' University Hospital (University of Cantabria), Santander, Spain.

    • Onofre Combarros
    •  & Ignacio Mateo
  89. Centro Investigacion Biomedica en Red Enfermedades Neurodegenerativas 'Marqués de Valdecilla' University Hospital (University of Cantabria), Santander, Spain.

    • Onofre Combarros
    • , Maria J Bullido
    • , Ignacio Mateo
    •  & Ana Frank-Garcia
  90. Centre National de Genotypage, Institut Genomique, Commissariat à l'énergie Atomique, Evry, France.

    • Diana Zelenika
    •  & Marc Delepine
  91. Centro de Biologia Molecular Severo Ochoa, Universidad Autonoma, Campus de Cantoblanco, Madrid, Spain.

    • Maria J Bullido
    •  & Philippe Amouyel
  92. Centre Hospitalier Régional Universitaire de Lille, Lille, France.

    • Florence Pasquier
  93. Servicio de Neurologia, Hospital Universitario La Paz (UAM), Madrid, Spain.

    • Ana Frank-Garcia
  94. Department of Experimental Pathology, School of Medicine, University of Bologna, Bologna, Italy.

    • Elisa Porcellini
    •  & Federico Licastro
  95. University Paris Descartes, Department of Geriatrics, Broca Hospital, Paris, France.

    • Olivier Hanon
  96. Genetic Molecular Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.

    • Eliecer Coto
    •  & Victoria Alvarez
  97. Istituto Di Ricovero e Cura a Carattere Scientifico Oasi Maria SS, Troina, Italy.

    • Paolo Bosco
  98. Department of Neuroscience, Neurological Clinic, University of Pisa, Italy.

    • Gabriele Siciliano
    •  & Michelangelo Mancuso
  99. Department of Geriatrics, Center for Aging Brain, Memory Unit, University of Bari, Policlinico, Bari, Italy.

    • Francesco Panza
    •  & Vincenzo Solfrizzi
  100. Department of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy.

    • Benedetta Nacmias
    •  & Sandro Sorbi
  101. Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Roma, Italy.

    • Paola Bossù
  102. Lab of Molecular Genetics, Section of Clinical Pharmacology, Department of Neuroscience, University of Cagliari, Cagliari, Italy.

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  103. Department of Internal Medicine, Università degli Studi di Milano, Fondazione IRCCS, Ospedale Maggiore, Mangiagalli e Regina Elena, Milan, Italy.

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  104. Department of Clinical Medicine and Prevention, University of Milano-Bicocca, Monza, Italy.

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  105. Geriatric Unit and Gerontology-Geriatric Research Laboratory, Department of Medical Science, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.

    • Davide Seripa
    •  & Alberto Pilotto
  106. Department of Neurological Sciences, Università degli Studi di Milano, Fondazione IRCCS, Ospedale Maggiore, Mangiagalli e Regina Elena, Milan, Italy.

    • Elio Scarpini
    •  & Daniela Galimberti
  107. INSERM, UMR_S679, Hopital de la salpétirère, Paris, France.

    • Alexis Brice
  108. INSERM U614, Faculté de Médecine-Pharmacie de Rouen, Rouen, France.

    • Didier Hannequin

Consortia

  1. the Alzheimer's Disease Neuroimaging Initiative

    Data used in the preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (see URLs). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. See URLs for a complete listing of the ADNI investigators.

  2. CHARGE consortium

  3. EADI1 consortium

Authors

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Contributions

J. Williams directed this study, assisted by M.J.O. and M.O.D. and was also helped by P.H., R.S., A.G., R.A., L.J. and D. Harold. J. Williams, P.H. and D.H. took primary responsibility for drafting the manuscript, assisted by R.S., A.G., R.A., M.O.D. and M.J.O. All authors contributed to the sample collection, sample preparation, genotyping and/or conduct of the GWAS upon which this study is based. J. Williams, R.A., P.H., R.S., A.G., C.W., J. Chapman, K.D., N.J., A.S., C. Thomas, S. Lovestone, J.P., P. Proitsi, M.K.L., C. Brayne, D.C.R., M.G., B.L., A.L., K. Morgan, K.S.B., P.A.P., D. Craig, B.M., S.T., C.H., D.M., A.D.S., S. Love, P.G.K., J.H., S. Mead, N.C.F., M. Rossor, J. Collinge, W.M., F.J., B.S., E.R., R.H., H.K., H.v.d.B., I.H., J.K., J. Wiltfang, M. Dichgans, L.F., H.H., M. Hüll, J.G., A.M.G., D.R., I.G., J.S.K.K., C.C., P.N., J.C.M., K. Mayo, K. Sleegers, K.B., S.E., P.P.D., C.V.B., G.L., N.J.B., H.G., A.M., M.T., T.W.M., M.M.N., S. Moebus, K.-H.J., N.K. and H.-E.W. contributed to clinical sample collection, ascertainment, diagnosis and preparation of samples from the independent GERAD2 sample genotyped as part of this study. R.S., D. Harold, A.G., D.R. and I.G. were responsible for procedures related to genotyping the GERAD2 sample. V.C., B.G.-B., M. Hiltunen, O.C., D.Z., M. Delepine, M.J.B., F. Pasquier, I.M., A.F.-G., E.P., O.H., E. Coto, V.A., P. Bosco, G.S., M. Mancuso, F. Panza, B.N., S. Sorbi, P. Bossù, P. Piccardi, B.A., G.A., D.S., E.S., D.G., A.B., D. Hannequin, F.L., H. Soininen, J.-C.L. and P.A. were responsible for sample collection, sample preparation, genotyping and analysis of the EADI2 Sample. S.S., A.L.D., O.L. and L.J.L., as well as M.A.I., C.M.v.D. and M.M.B.B. contributed clinical and genotypic data to the CHARGE GWAS. J.-C.L. and P.A. contributed clinical and genotypic data. M.M.C. played a leading role, along with H.B., D.W., G.W., N.M.H., E.R.L.C.V., S.B.S., J.O.A., M.B., Z.K.W., D.W.D., N.R.G.R., R.C.P., K. Morgan and S.G.Y. in sample collection, sample preparation, genotyping and analysis of the Mayo2 sample. M. Riemenschneider, T.M.F., P.F., C.R., M.K., S. Schreiber, M. Mayhaus, S.N. and S.W. were responsible for sample collection, conduct and analysis of the AD-IG GWAS. S. Steinberg, T.J., H. Stefansson, K. Stefansson, J.S., S.B. and P.V.J were responsible for sample collection, conduct and analysis of the deCODE GWAS. D. Harold and P.H. completed statistical quality control and produced association statistics under the supervision of J. Williams and P.A.H. All authors discussed the results and approved the manuscript.

Competing interests

The authors have applied for an International PCT (Patent Co-operation Treaty) patent filing (European Office).

Corresponding authors

Correspondence to Michael J Owen or Julie Williams.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Note and Supplementary Tables 1–5

Excel files

  1. 1.

    Supplementary Table 6

    Results for SNPs at the CD2AP, EPHA1, ARID5B and CD33 loci.

  2. 2.

    Supplementary Table 7

    Sample size tested for each SNP

  3. 3.

    Supplementary Table 8

    Summary statistics for each dataset

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/ng.803

Further reading