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PMID: 19734902 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

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

Nature genetics ·Vol. 41 ·No. 10 ·2009-10-00 ·Pages 1088-93

Harold D, Abraham R, Hollingworth P, Sims R, Gerrish A, Hamshere ML, Pahwa JS, Moskvina V, Dowzell K, Williams A, Jones N, Thomas C, Stretton A, Morgan AR, Lovestone S, Powell J, Proitsi P, Lupton MK, Brayne C, Rubinsztein DC, Gill M, Lawlor B, Lynch A, Morgan K, Brown KS, Passmore PA, Craig D, McGuinness B, Todd S, Holmes C, Mann D, Smith AD, Love S, Kehoe PG, Hardy J, Mead S, Fox N, Rossor M, Collinge J, Maier W, Jessen F, Schürmann B, Heun R, van den Bussche H, Heuser I, Kornhuber J, Wiltfang J, Dichgans M, Frölich L, Hampel H, Hüll M, Rujescu D, Goate AM, Kauwe JS, Cruchaga C, Nowotny P, Morris JC, Mayo K, Sleegers K, Bettens K, Engelborghs S, De Deyn PP, Van Broeckhoven C, Livingston G, Bass NJ, Gurling H, McQuillin A, Gwilliam R, Deloukas P, Al-Chalabi A, Shaw CE, Tsolaki M, Singleton AB, Guerreiro R, Mühleisen TW, Nöthen MM, Moebus S, Jöckel KH, Klopp N, Wichmann HE, Carrasquillo MM, Pankratz VS, Younkin SG, Holmans PA, O'Donovan M, Owen MJ, Williams J

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 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).

MeSH Terms
Alzheimer Disease/genetics Chromosomes, Human Clusterin/genetics Genetic Predisposition to Disease Genome, Human Genome-Wide Association Study Humans Monomeric Clathrin Assembly Proteins/genetics Polymorphism, Single Nucleotide
Chemicals
CLU protein, human Clusterin Monomeric Clathrin Assembly Proteins PICALM protein, human
Authors & Affiliations
87 authors, click to expand affiliations / ORCID
Harold Denise
Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK.
Abraham Richard
Hollingworth Paul
Sims Rebecca
Gerrish Amy
Hamshere Marian L
Pahwa Jaspreet Singh
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
Rossor Martin
Collinge John
Maier Wolfgang
Jessen Frank
Schürmann Britta
Heun Reinhard
van den Bussche Hendrik
Heuser Isabella
Kornhuber Johannes
Wiltfang Jens
Dichgans Martin
Frölich Lutz
Hampel Harald
Hüll Michael
Rujescu Dan
Goate Alison M
Kauwe John S K
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
Mühleisen Thomas W
Nöthen Markus M
Moebus Susanne
Jöckel 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
Williams Julie
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.440
Published
2009-10-00
Epub
2009-00-06
Pages
1088-93
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC2845877
Subset
IM
Grants
Medical Research Council · MC_U123192748 · United Kingdom
Medical Research Council · MC_U123160651 · United Kingdom
Medical Research Council · G0701075 · United Kingdom
Medical Research Council · G0600974 · United Kingdom
NCRR NIH HHS · UL1 RR024992 · United States
Wellcome Trust · 064354 · United Kingdom
Medical Research Council · G0900688 · United Kingdom
Medical Research Council · G0801418 · United Kingdom
Medical Research Council · G0300429 · United Kingdom
Wellcome Trust · 082604 · United Kingdom
Medical Research Council · G0601846 · United Kingdom
Intramural NIH HHS · United States
Corrections
ErratumIn
-
ErratumIn
-
CommentIn
PMID: 19786950
External Links
PubMed source DOI: 10.1038/ng.440 PMC Full Text View journal details
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