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), 1088-1093. (doi:10.1038/ng.440).


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Original Publication URL: http://dx.doi.org/10.1038/ng.440


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)
Related URLs:
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions : University Structure - Pre August 2011 > School of Medicine > Clinical Neurosciences
ePrint ID: 73445
Accepted Date and Publication Date:
Date Deposited: 05 Mar 2010
Last Modified: 31 Mar 2016 13:06
URI: http://eprints.soton.ac.uk/id/eprint/73445

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