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

Harold, Denise, Abraham, Richard, Hollingworth, Paul, Sims, Rebecca, Gerrish, Amy, Hamshere, Marian L., Pahwa, Jaspreet Sing, 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, Rosser, Martin, Collinge, John, Maier, Wolfgang, Jessen, Frank, Schurmann, Britta, Van den Bussche, Hendrick, Heuser, Isabella, Kornhuber, Johannes, Wiltfang, Jens, Dichgans, Martin, Frolich, Lutz, Hampel, Harald, Hull, Michael, Rujescu, Dan, Goate, Alison M., Kauwe, John S., Cruchaga, Carlos, Nowotny, Petra, Morris, John C., Mayo, Kevin, Sleegers, Kristel, Bettens, Karolien, Engelborghs, Sebastiaan, De Deyn, Peter P., Van Broeckhoven, Christine, Livingston, Gill, Bass, Nicholas J., Gurling, Hugh, McQuillin, Andrew, Gwilliam, Rhian, Deloukas, Panagiotis, Al-Chalabi, Ammar, Shaw, Christopher E., Tsolaki, Magda, Singleton, Andrew B., Guerreiro, Rita, Muhleisen, Thomas W., Nothen, Markus M., Moebus, Susanne, Jockel, Karl Heinz, Klopp, Norman, Wichmann, H.Erich, Carrasquillo, Minerva M, Pankratz, V.Shane, Younkin, Steven G., Holmans, Peter A., O'Donovan, Michael, Owen, Michael J. and Williams, Julie (2009) Letter abstract - Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's Disease Nature Genetics, 41, (10), pp. 1088-1093. (doi:10.1038/ng.440).


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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).

Item Type: Article
Digital Object Identifier (DOI): doi:10.1038/ng.440
ISSNs: 1061-4036 (print)
ePrint ID: 73445
Date :
Date Event
Date Deposited: 05 Mar 2010
Last Modified: 18 Apr 2017 20:51
Further Information:Google Scholar
URI: http://eprints.soton.ac.uk/id/eprint/73445

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