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Genetic Evidence Implicates the Immune System and Cholesterol Metabolism in the Aetiology of Alzheimer's Disease

  • Lesley Jones equal contributor,

    equal contributor Contributed equally to this work with: Lesley Jones, Peter A. Holmans

    Affiliation: Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, United Kingdom

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  • Peter A. Holmans equal contributor,

    equal contributor Contributed equally to this work with: Lesley Jones, Peter A. Holmans

    Affiliation: Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, United Kingdom

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  • Marian L. Hamshere,

    Affiliation: Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, United Kingdom

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  • Denise Harold,

    Affiliation: Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, United Kingdom

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  • Valentina Moskvina,

    Affiliation: Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, United Kingdom

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  • Dobril Ivanov,

    Affiliation: Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, United Kingdom

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  • Andrew Pocklington,

    Affiliation: Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, United Kingdom

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  • Richard Abraham,

    Affiliation: Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, United Kingdom

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  • Paul Hollingworth,

    Affiliation: Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, United Kingdom

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  • Rebecca Sims,

    Affiliation: Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, United Kingdom

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  • Amy Gerrish,

    Affiliation: Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, United Kingdom

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  • Jaspreet Singh Pahwa,

    Affiliation: Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, United Kingdom

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  • Nicola Jones,

    Affiliation: Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, United Kingdom

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  • Alexandra Stretton,

    Affiliation: Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, United Kingdom

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  • Angharad R. Morgan,

    Affiliation: Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, United Kingdom

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  • Simon Lovestone,

    Affiliation: 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, United Kingdom

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  • John Powell,

    Affiliation: Department of Neuroscience, Institute of Psychiatry, Kings College, London, United Kingdom

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  • Petroula Proitsi,

    Affiliation: Department of Neuroscience, Institute of Psychiatry, Kings College, London, United Kingdom

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  • Michelle K. Lupton,

    Affiliation: Department of Neuroscience, Institute of Psychiatry, Kings College, London, United Kingdom

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  • Carol Brayne,

    Affiliation: Institute of Public Health, University of Cambridge, Cambridge, United Kingdom

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  • David C. Rubinsztein,

    Affiliation: Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom

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  • Michael Gill,

    Affiliation: Mercer's Institute for Research on Aging, St. James Hospital and Trinity College, Dublin, Ireland

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  • Brian Lawlor,

    Affiliation: Mercer's Institute for Research on Aging, St. James Hospital and Trinity College, Dublin, Ireland

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  • Aoibhinn Lynch,

    Affiliation: Mercer's Institute for Research on Aging, St. James Hospital and Trinity College, Dublin, Ireland

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  • Kevin Morgan,

    Affiliation: Institute of Genetics, Queen's Medical Centre, University of Nottingham, Nottingham, United Kingdom

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  • Kristelle S. Brown,

    Affiliation: Institute of Genetics, Queen's Medical Centre, University of Nottingham, Nottingham, United Kingdom

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  • Peter A. Passmore,

    Affiliation: Ageing Group, Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, United Kingdom

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  • David Craig,

    Affiliation: Ageing Group, Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, United Kingdom

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  • Bernadette McGuinness,

    Affiliation: Ageing Group, Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, United Kingdom

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  • Stephen Todd,

    Affiliation: Ageing Group, Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, United Kingdom

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  • Clive Holmes,

    Affiliation: Division of Clinical Neurosciences, School of Medicine, University of Southampton, Southampton, United Kingdom

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  • David Mann,

    Affiliation: Clinical Neuroscience Research Group, Greater Manchester Neurosciences Centre, University of Manchester, Salford, United Kingdom

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  • A. David Smith,

    Affiliation: Oxford Project to Investigate Memory and Ageing, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom

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  • Seth Love,

    Affiliation: Dementia Research Group, University of Bristol Institute of Clinical Neurosciences, Frenchay Hospital, Bristol, United Kingdom

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  • Patrick G. Kehoe,

    Affiliation: Dementia Research Group, University of Bristol Institute of Clinical Neurosciences, Frenchay Hospital, Bristol, United Kingdom

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  • Simon Mead,

    Affiliation: MRC Prion Unit, Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, United Kingdom

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  • Nick Fox,

    Affiliation: Dementia Research Centre, Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, United Kingdom

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  • Martin Rossor,

    Affiliation: Dementia Research Centre, Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, United Kingdom

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  • John Collinge,

    Affiliation: MRC Prion Unit, Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, United Kingdom

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  • Wolfgang Maier,

    Affiliation: Department of Psychiatry, University of Bonn, Bonn, Germany

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  • Frank Jessen,

    Affiliation: Department of Psychiatry, University of Bonn, Bonn, Germany

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  • Britta Schürmann,

    Affiliation: Department of Psychiatry, University of Bonn, Bonn, Germany

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  • Hendrik van den Bussche,

    Affiliation: Institute of Primary Medical Care, University Medical Center Hamburg-Eppendorf, Germany

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  • Isabella Heuser,

    Affiliation: Institute of Primary Medical Care, University Medical Center Hamburg-Eppendorf, Germany

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  • Oliver Peters,

    Affiliation: Institute of Primary Medical Care, University Medical Center Hamburg-Eppendorf, Germany

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  • Johannes Kornhuber,

    Affiliation: Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Erlangen, Germany

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  • Jens Wiltfang,

    Affiliation: Landschaftsverband Rheinland-Hospital Essen, Department of Psychiatry and Psychotherapy, University Duisburg-Essen, Essen, Germany

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  • Martin Dichgans,

    Affiliations: Institute for Stroke and Dementia Research, Klinikum der Universität München, Munich, Germany, Department of Neurology, Klinikum der Universität München, Munich, Germany

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  • Lutz Frölich,

    Affiliation: Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

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  • Harald Hampel,

    Affiliations: Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Laboratory of Neuroimaging and Biomarker Research, Trinity College, University of Dublin, Dublin, Ireland, Alzheimer Memorial Center and Geriatric Psychiatry Branch, Department of Psychiatry, Ludwig-Maximilian University, Munich, Germany

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  • Michael Hüll,

    Affiliation: Centre for Geriatric Medicine and Section of Gerontopsychiatry and Neuropsychology, Medical School, University of Freiburg, Freiburg, Germany

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  • Dan Rujescu,

    Affiliation: Alzheimer Memorial Center and Geriatric Psychiatry Branch, Department of Psychiatry, Ludwig-Maximilian University, Munich, Germany

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  • Alison M. Goate,

    Affiliation: Departments of Psychiatry, Neurology and Genetics, Washington University School of Medicine, St. Louis, Missouri, United States of America

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  • John S. K. Kauwe,

    Affiliation: Department of Biology, Brigham Young University, Provo, Utah, United States of America

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  • Carlos Cruchaga,

    Affiliation: Departments of Psychiatry, Neurology and Genetics, Washington University School of Medicine, St. Louis, Missouri, United States of America

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  • Petra Nowotny,

    Affiliation: Departments of Psychiatry, Neurology and Genetics, Washington University School of Medicine, St. Louis, Missouri, United States of America

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  • John C. Morris,

    Affiliation: Departments of Psychiatry, Neurology and Genetics, Washington University School of Medicine, St. Louis, Missouri, United States of America

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  • Kevin Mayo,

    Affiliation: Departments of Psychiatry, Neurology and Genetics, Washington University School of Medicine, St. Louis, Missouri, United States of America

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  • Gill Livingston,

    Affiliation: Department of Mental Health Sciences, UCL, London, United Kingdom

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  • Nicholas J. Bass,

    Affiliation: Department of Mental Health Sciences, UCL, London, United Kingdom

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  • Hugh Gurling,

    Affiliation: Department of Mental Health Sciences, UCL, London, United Kingdom

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  • Andrew McQuillin,

    Affiliation: Department of Mental Health Sciences, UCL, London, United Kingdom

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  • Rhian Gwilliam,

    Affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom

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  • Panos Deloukas,

    Affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom

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  • Ammar Al-Chalabi,

    Affiliation: MRC Centre for Neurodegeneration Research, Department of Clinical Neuroscience, King's College London, Institute of Psychiatry, London, United Kingdom

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  • Christopher E. Shaw,

    Affiliation: MRC Centre for Neurodegeneration Research, Department of Clinical Neuroscience, King's College London, Institute of Psychiatry, London, United Kingdom

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  • Andrew B. Singleton,

    Affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America

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  • Rita Guerreiro,

    Affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America

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  • Thomas W. Mühleisen,

    Affiliations: Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany, Institute of Human Genetics, University of Bonn, Bonn, Germany

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  • Markus M. Nöthen,

    Affiliations: Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany, Institute of Human Genetics, University of Bonn, Bonn, Germany

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  • Susanne Moebus,

    Affiliation: Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany

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  • Karl-Heinz Jöckel,

    Affiliation: Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany

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  • Norman Klopp,

    Affiliation: Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

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  • H.-Erich Wichmann,

    Affiliations: Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany, Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany, Klinikum Grosshadern, Munich, Germany

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  • Eckhard Rüther,

    Affiliation: Department of Psychiatry, University of Gottingen, Gottingen, Germany

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  • Minerva M. Carrasquillo,

    Affiliation: Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida, United States of America

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  • V. Shane Pankratz,

    Affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, United States of America

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  • Steven G. Younkin,

    Affiliation: Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida, United States of America

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  • John Hardy,

    Affiliation: Department of Molecular Neuroscience and Reta Lilla Weston Laboratories, Institute of Neurology, London, United Kingdom

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  • Michael C. O'Donovan,

    Affiliation: Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, United Kingdom

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  • Michael J. Owen mail,

    williamsj@cf.ac.uk (JW); owenmj@cf.ac.uk (MJO)

    Affiliation: Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, United Kingdom

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  • Julie Williams mail

    williamsj@cf.ac.uk (JW); owenmj@cf.ac.uk (MJO)

    Affiliation: Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, United Kingdom

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  • Published: November 15, 2010
  • DOI: 10.1371/journal.pone.0013950

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