| Autor: |
Seshadri, S, Fitzpatrick, AL, Ikram, Arfan, DeStefano, AL, Gudnason, V, Boada, M, Bis, JC, Smith, AV, Carassquillo, MM, Lambert, JC, Harold, D, Schrijvers, Elisabeth, Ramirez-Lorca, R, Debette, S, Longstreth, WT, Janssens, Cecile, Pankratz, VS, Dartigues, JF, Hollingworth, P, Aspelund, T, Hernandez, I, Beiser, A, Kuller, LH, Koudstaal, Peter, Dickson, DW, Tzourio, C, Abraham, R, Antunez, C, Du, YC, Rotter, JI, Aulchenko, YS, Harris, TB, Petersen, RC, Berr, C, Owen, MJ, Lopez-Arrieta, J, Varadarajan, BN, Becker, JT, Rivadeneira, Fernando, Nalls, MA, Graff-Radford, NR, Campion, D, Auerbach, S, Rice, K, Hofman, Bert, Jonsson, PV, Schmidt, Heléna, Lathrop, M, Mosley, TH, Psaty, BM, Uitterlinden, André, Farrer, LA, Lumley, T, Ruiz, A, Williams, J, Amouyel, P, Younkin, SG, Wolf, PA, Launer, LJ (Lenore), Lopez, OL, Duijn, Cornelia, Breteler, Monique |
| Přispěvatelé: |
Radiology & Nuclear Medicine, Epidemiology, Neurology, Internal Medicine |
| Rok vydání: |
2010 |
| Zdroj: |
JAMA-Journal of the American Medical Association, 303(18), 1832-1840. American Medical Association |
| ISSN: |
0098-7484 |
| Popis: |
Context Genome-wide association studies (GWAS) have recently identified CLU, PICALM, and CR1 as novel genes for late-onset Alzheimer disease (AD). Objectives To identify and strengthen additional loci associated with AD and confirm these in an independent sample and to examine the contribution of recently identified genes to AD risk prediction in a 3-stage analysis of new and previously published GWAS on more than 35 000 persons (8371 AD cases). Design, Setting, and Participants In stage 1, we identified strong genetic associations (P < 10(-3)) in a sample of 3006 AD cases and 14 642 controls by combining new data from the population-based Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (1367 AD cases [973 incident]) with previously reported results from the Translational Genomics Research Institute and the Mayo AD GWAS. We identified 2708 single-nucleotide polymorphisms (SNPs) with P < 10(-3). In stage 2, we pooled results for these SNPs with the European AD Initiative (2032 cases and 5328 controls) to identify 38 SNPs (10 loci) with P < 10(-5). In stage 3, we combined data for these 10 loci with data from the Genetic and Environmental Risk in AD consortium (3333 cases and 6995 controls) to identify 4 SNPs with P < 1.7 x 10(-8). These 4 SNPs were replicated in an independent Spanish sample (1140 AD cases and 1209 controls). Genome-wide association analyses were completed in 2007-2008 and the meta-analyses and replication in 2009. Main Outcome Measure Presence of Alzheimer disease. Results Two loci were identified to have genome-wide significance for the first time: rs744373 near BIN1 (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.06-1.21 per copy of the minor allele; P=1.59 x 10(-11)) and rs597668 near EXOC3L2/BLOC1S3/MARK4 (OR, 1.18; 95% CI, 1.07-1.29; P=6.45 x 10(-9)). Associations of these 2 loci plus the previously identified loci CLU and PICALM with AD were confirmed in the Spanish sample (P |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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