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

TitleGenome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2009
AuthorsHarold D, Abraham R, Hollingworth P, Sims R, Gerrish A, Hamshere ML, Pahwa JSingh, 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, A Smith D, 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 JSK, 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 K-H, Klopp N, Wichmann H-E, Carrasquillo MM, V Pankratz S, Younkin SG, Holmans PA, O'Donovan M, Owen MJ, Williams J
JournalNat Genet
Volume41
Issue10
Pagination1088-93
Date Published2009 Oct
ISSN1546-1718
KeywordsAlzheimer Disease, Chromosomes, Human, Clusterin, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Humans, Monomeric Clathrin Assembly Proteins, Polymorphism, Single Nucleotide
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).

DOI10.1038/ng.440
Alternate JournalNat. Genet.
PubMed ID19734902
PubMed Central IDPMC2845877
Grant ListMC_U123192748 / / Medical Research Council / United Kingdom
MC_U123160651 / / Medical Research Council / United Kingdom
G0701075 / / Medical Research Council / United Kingdom
G0600974 / / Medical Research Council / United Kingdom
/ / Medical Research Council / United Kingdom
G0300429 / / Medical Research Council / United Kingdom
082604 / / Wellcome Trust / United Kingdom
UL1 RR024992 / RR / NCRR NIH HHS / United States
/ / Intramural NIH HHS / United States
064354 / / Wellcome Trust / United Kingdom
G0900688 / / Medical Research Council / United Kingdom
G0601846 / / Medical Research Council / United Kingdom
G0801418 / / Medical Research Council / United Kingdom
/ / Wellcome Trust / United Kingdom