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

Denise D Harold, Richard R Abraham, Paul P Hollingworth, Rebecca R Sims, Amy A Gerrish, Marian L ML Hamshere, Jaspreet Singh JS Pahwa, Valentina V Moskvina, Kimberley K Dowzell, Amy A Williams, Nicola N Jones, Charlene C Thomas, Alexandra A Stretton, Angharad R AR Morgan, Simon S Lovestone, John J Powell, Petroula P Proitsi, Michelle K MK Lupton, Carol C Brayne, David C DC Rubinsztein, Michael M Gill, Brian B Lawlor, Aoibhinn A Lynch, Kevin K Morgan, Kristelle S KS Brown, Peter A PA Passmore, David D Craig, Bernadette B McGuinness, Stephen S Todd, Clive C Holmes, David D Mann, A David AD Smith, Seth S Love, Patrick G PG Kehoe, John J Hardy, Simon S Mead, Nick N Fox, Martin M Rossor, John J Collinge, Wolfgang W Maier, Frank F Jessen, Britta B Schürmann, Hendrik H van den Bussche, Isabella I Heuser, Johannes J Kornhuber, Jens J Wiltfang, Martin M Dichgans, Lutz L Frölich, Harald H Hampel, Michael M Hüll, Dan D Rujescu, Alison M AM Goate, John S K JS Kauwe, Carlos C Cruchaga, Petra P Nowotny, John C JC Morris, Kevin K Mayo, Kristel K Sleegers, Karolien K Bettens, Sebastiaan S Engelborghs, Peter P PP De Deyn, Christine C Van Broeckhoven, Gill G Livingston, Nicholas J NJ Bass, Hugh H Gurling, Andrew A McQuillin, Rhian R Gwilliam, Panagiotis P Deloukas, Ammar A Al-Chalabi, Christopher E CE Shaw, Magda M Tsolaki, Andrew B AB Singleton, Rita R Guerreiro, Thomas W TW Mühleisen, Markus M MM Nöthen, Susanne S Moebus, Karl-Heinz KH Jöckel, Norman N Klopp, H-Erich HE Wichmann, Minerva M MM Carrasquillo, V Shane VS Pankratz, Steven G SG Younkin, Peter A PA Holmans, Michael M O'Donovan, Michael J MJ Owen, and Julie J Williams

Audio, Transactions of the IRE Professi... 41(10):1088-93 (2009) PMID 19734902

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).

DOI: 10.1038/ng.440
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