Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease

D. Harold, R. Abraham, P. Hollingworth, R. Sims, A. Gerrish, M.L. Hamshere, J.S. Pahwa, V. Moskvina, K. Dowzell, A. Williams, N. Jones, C. Thomas, A. Stretton, A.R. Morgan, S. Lovestone, J. Powell, P. Proitsi, M.K. Lupton, C. Brayne, D.C. RubinszteinM. Gill, B. Lawlor, A. Lynch, K. Morgan, K.S. Brown, Peter A. Passmore, David Craig, Bernadette McGuinness, Stephen Todd, C. Holmes, D. Mann, A.D. Smith, S. Love, P.G. Kehoe, J. Hardy, S. Mead, N. Fox, M. Rossor, J. Collinge, W. Maier, F. Jessen, B. Schurmann, H. Van Den Bussche, I. Heuser, J. Kornhuber, J. Wiltfang, M. Dichgans, L. Frolich, H. Hampel, M. Hull, D. Rujescu, A.M. Goate, J.S.K. Kauwe, C. Cruchaga, P. Nowotny, J.C. Morris, K. Mayo, K. Sleegers, K. Bettens, S. Engelborghs, P.P. De Deyn, C. Van Broeckhoven, G. Livingston, N.J. Bass, H. Gurling, A. McQuillin, R. Gwilliam, P. Deloukas, A. Al-Chalabi, C.E. Shaw, M. Tsolaki, A.B. Singleton, R. Guerreiro, T.W. Muhleisen, M.M. Nothen, S. Moebus, K.H. Jockel, N. Klopp, H.E. Wichmann, M.M. Carrasquillo, V.S. Pankratz, S.G. Younkin, P.A. Holmans, M. O'Donovan, M.J. Owen, J. Williams

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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 × 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 × 10−9) and 5′ to the PICALM gene (rs3851179, P = 1.9 × 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 × 10−10, odds ratio = 0.86; rs3851179, P = 1.3 × 10−9, odds ratio = 0.86).

Original languageEnglish
Pages (from-to)1088-1093
Number of pages6
JournalNature Genetics
Issue number10
Early online date06 Sep 2009
Publication statusPublished - 02 Oct 2009

ASJC Scopus subject areas

  • Genetics


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