Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease.
| Title | Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. |
| Publication Type | Journal Article |
| Year of Publication | 2009 |
| Authors | Harold, 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 |
| Journal | Nat Genet |
| Volume | 41 |
| Issue | 10 |
| Pagination | 1088-93 |
| Date Published | 2009 Oct |
| ISSN | 1546-1718 |
| Keywords | Alzheimer 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). |
| DOI | 10.1038/ng.440 |
| Alternate Journal | Nat. Genet. |
| PubMed ID | 19734902 |
| PubMed Central ID | PMC2845877 |
| Grant List | MC_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 |