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Nature Genetics 41, 1088–1093 (1 October 2009) | doi:10.1038/ng.440

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

Denise Harold , Richard Abraham , Paul Hollingworth , Rebecca Sims , Amy Gerrish , Marian L Hamshere , Jaspreet Singh Pahwa , Valentina Moskvina , Kimberley Dowzell , Amy Williams , Nicola Jones , Charlene Thomas , Alexandra Stretton , Angharad R Morgan , Simon Lovestone , John Powell , Petroula Proitsi , Michelle K Lupton , Carol Brayne , David C Rubinsztein , Michael Gill , Brian Lawlor , Aoibhinn Lynch , Kevin Morgan , Kristelle S Brown , Peter A Passmore , David Craig , Bernadette McGuinness , Stephen Todd , Clive Holmes , David Mann , A David Smith , Seth Love , Patrick G Kehoe , John Hardy , Simon Mead , Nick Fox , Martin Rossor , John Collinge , Wolfgang Maier , Frank Jessen , Britta Sch|[uuml]|rmann , Hendrik van den Bussche , Isabella Heuser , Johannes Kornhuber , Jens Wiltfang , Martin Dichgans , Lutz Fr|[ouml]|lich , Harald Hampel , Michael H|[uuml]|ll , Dan Rujescu , Alison M Goate , John S K Kauwe , Carlos Cruchaga , Petra Nowotny , John C Morris , Kevin Mayo , Kristel Sleegers , Karolien Bettens , Sebastiaan Engelborghs , Peter P De Deyn , Christine Van Broeckhoven , Gill Livingston , Nicholas J Bass , Hugh Gurling , Andrew McQuillin , Rhian Gwilliam , Panagiotis Deloukas , Ammar Al-Chalabi , Christopher E Shaw , Magda Tsolaki , Andrew B Singleton , Rita Guerreiro , Thomas W M|[uuml]|hleisen , Markus M N|[ouml]|then , Susanne Moebus , Karl-Heinz J|[ouml]|ckel , Norman Klopp , H-Erich Wichmann , Minerva M Carrasquillo , V Shane Pankratz , Steven G Younkin , Peter A Holmans , Michael O'Donovan , Michael J Owen & Julie Williams

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 |[times]| 10|[minus]|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 |[times]| 10|[minus]|9) and 5|[prime]| to the PICALM gene (rs3851179, P = 1.9 |[times]| 10|[minus]|8).