Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease (vol 41, pg 1088, 2009)

被引：13

作者：

Harold, Denise

Abraham, Richard

Hollingworth, Paul

Sims, Rebecca

Gerrish, Amy

Hamshere, Marian L.

Pahwa, Jaspreet Singh

Moskvina, Valentina

Dowzell, Kimberley

Williams, Amy

Jones, Nicola

Thomas, Charlene

Stretton, Alexandra

Morgan, Angharad R.

Lovestone, Simon

Powell, John

Proitsi, Petroula

Lupton, Michelle K.

Brayne, Carol

Rubinsztein, David C.

Gill, Michael

Lawlor, Brian

Lynch, Aoibhinn

Morgan, Kevin

Brown, Kristelle S.

Passmore, Peter A.

Craig, David

McGuinness, Bernadette

Todd, Stephen

Holmes, Clive

Mann, David

Smith, A. David

Love, Seth

Kehoe, Patrick G.

Hardy, John

Mead, Simon

Fox, Nick

Rossor, Martin

Collinge, John

Maier, Wolfgang

Jessen, Frank

Schuermann, Britta

van den Bussche, Hendrik

Heuser, Isabella

Kornhuber, Johannes

Wiltfang, Jens

Dichgans, Martin

Froelich, Lutz

Hampel, Harald

Huell, Michael

机构：

[1] Department of Psychological Medicine and Neurology, Medical Research Council (MRC), Cardiff University, Cardiff

[2] National Institute for Health Research Biomedical Research Centre for Mental Health, South London and Maudsley National Health Service Foundation Trust, Institute of Psychiatry, London

[3] Department of Neuroscience, Institute of Psychiatry, Kings College, London

[4] Cambridge Institute for Medical Research, University of Cambridge, Cambridge

[5] Mercer's Institute for Research on Aging, St. James Hospital and Trinity College, Dublin

[6] Institute of Genetics, Queen's Medical Centre, University of Nottingham, Nottingham

[7] Centre for Public Health, School of Medicine, Queen's University Belfast, Belfast

[8] Division of Clinical Neurosciences, School of Medicine, University of Southampton, Southampton

[9] Clinical Neuroscience Research Group, Greater Manchester Neurosciences Centre, University of Manchester, Salford

[10] Oxford Project to Investigate Memory and Ageing, University of Oxford, John Radcliffe Hospital, Oxford

[11] Dementia Research Group, University of Bristol Institute of Clinical Neurosciences, Frenchay Hospital, Bristol

[12] Department of Molecular Neuroscience, Reta Lilla Weston Laboratories, Institute of Neurology, London

[13] 15Dementia Research Centre, Department of Neurodegenerative Diseases, UCL Institute of Neurology, London

[14] Department of Psychiatry, University of Bonn, Bonn

[15] Institute of Primary Medical Care, University Medical Center Hamburg-Eppendorf, Hamburg

[16] Department of Psychiatry, Charité Berlin, Berlin

[17] Department of Psychiatry and Psychotherapy, University of Erlangen-Nürnberg, Erlangen

[18] Landschaftsverband Rheinland-Hospital Essen, Department of Psychiatry and Psychotherapy, University Duisburg-Essen, Essen

[19] Department of Neurology, Klinikum der Universität München, Munich

[20] Department of Geriatric Psychiatry, Central Institute of Mental Health, University of Heidelberg, Mannheim

[21] School of Medicine, Trinity College Institute of Neuroscience, University of Dublin, Dublin

[22] Department of Psychiatry, Alzheimer Memorial Center, Ludwig-Maximilian University, Munich

[23] Centre for Geriatric Medicine, Medical School, University of Freiburg, Freiburg

[24] Departments of Psychiatry, Neurology and Genetics, Washington University School of Medicine, St. Louis, MI

[25] Department of Biology, Brigham Young University, Provo, UT

[26] Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen

[27] Institute Born-Bunge, University of Antwerp, Antwerpen

[28] Memory Clinic and Department of Neurology, Ziekenhuis Netwerk Antwerpen Middelheim, Antwerpen

[29] Department of Mental Health Sciences, University College London, London

[30] Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge

[31] Department of Clinical Neuroscience, King's College London, Institute of Psychiatry, London

[32] Third Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki

[33] Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD

[34] Department of Genomics, Life and Brain Center

[35] Institute for Medical Informatics, University Hospital of Essen, University Duisburg-Essen, Essen

[36] Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg

[37] Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich

[38] Klinikum Grosshadern, Munich

[39] Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL

[40] Division of Biomedical Statistics and Informatics, Mayo Clinic and Mayo Foundation, Rochester, MI

来源：

NATURE GENETICS | 2009年 / 41卷 / 10期

关键词：

D O I：

10.1038/ng1009-1156d

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We undertook a two-stage genome-wide association study (GWAS) of Alzheimer's disease (AD) involving over 16,000 individuals, the most powerful AD GWAS to date. In stage 1 (3,941 cases and 7,848 controls), we replicated the established association with the apolipoprotein E (APOE) locus (most significant SNP, rs2075650, P = 1.8 x 10(-157)) and observed genome-wide significant association with SNPs at two loci not previously associated with the disease: at the CLU (also known as APOJ) gene (rs11136000, P = 1.4 x 10(-9)) and 5. to the PICALM gene (rs3851179, P = 1.9 x 10(-8)). These associations were replicated in stage 2 (2,023 cases and 2,340 controls), producing compelling evidence for association with Alzheimer's disease in the combined dataset (rs11136000, P = 8.5 x 10(-10), odds ratio = 0.86; rs3851179, P = 1.3 x 10(-9), odds ratio = 0.86).

引用

页码：1156 / 1156

页数：1