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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).

Record type: Article

Abstract

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).

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Published date: 2009

Identifiers

Local EPrints ID: 73445
URI: http://eprints.soton.ac.uk/id/eprint/73445
ISSN: 1061-4036
PURE UUID: 107d53ce-8a59-4923-88cf-797c429508cb

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Date deposited: 05 Mar 2010
Last modified: 18 Jul 2017 23:50

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Contributors

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

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