Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.

Abstract

Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10(-8)) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.

• Authors: J C Lambert, C A Ibrahim-Verbaas, D Harold, A C Naj, R Sims, C Bellenguez, A L DeStafano, J C Bis, G W Beecham, B Grenier-Boley, G Russo, T A Thorton-Wells, N Jones, A V Smith, V Chouraki, C Thomas, M A Ikram, D Zelenika, B N Vardarajan, Y Kamatani, C F Lin, A Gerrish, H Schmidt, B Kunkle, M L Dunstan, A Ruiz, M T Bihoreau, S H Choi, C Reitz, F Pasquier, C Cruchaga, D Craig, N Amin, C Berr, O L Lopez, P L De Jager, V Deramecourt, J A Johnston, D Evans, S Lovestone, L Letenneur, F J Morón, D C Rubinsztein, G Eiriksdottir, K Sleegers, A M Goate, N Fiévet, M W Huentelman, M Gill, K Brown, M I Kamboh, L Keller, P Barberger-Gateau, B McGuiness, E B Larson, R Green, A J Myers, C Dufouil, S Todd, D Wallon, S Love, E Rogaeva, J Gallacher, P St George-Hyslop, J Clarimon, A Lleo, A Bayer, D W Tsuang, L Yu, M Tsolaki, P Bossù, G Spalletta, P Proitsi, J Collinge, S Sorbi, F Sanchez-Garcia, N C Fox, J Hardy, M C Deniz Naranjo, P Bosco, R Clarke, C Brayne, D Galimberti, M Mancuso, F Matthews, European Alzheimer's Disease Initiative (EADI), Genetic and Environmental Risk in Alzheimer's Disease, Alzheimer's Disease Genetic Consortium, Cohorts for Heart and Aging Research in Genomic Epidemiology, S Moebus, P Mecocci, M Del Zompo, W Maier, H Hampel, A Pilotto, M Bullido, F Panza, P Caffarra, B Nacmias, J R Gilbert, M Mayhaus, L Lannefelt, H Hakonarson, S Pichler, M M Carrasquillo, M Ingelsson, D Beekly, V Alvarez, F Zou, O Valladares, S G Younkin, E Coto, K L Hamilton-Nelson, W Gu, C Razquin, P Pastor, I Mateo, M J Owen, K M Faber, P V Jonsson, O Combarros, M C O'Donovan, L B Cantwell, H Soininen, D Blacker, S Mead, T H Mosley Jr, D A Bennett, T B Harris, L Fratiglioni, C Holmes, R F de Bruijn, P Passmore, T J Montine, K Bettens, J I Rotter, A Brice, K Morgan, T M Foroud, W A Kukull, D Hannequin, J F Powell, M A Nalls, K Ritchie, K L Lunetta, J S Kauwe, E Boerwinkle, M Riemenschneider, M Boada, M Hiltuenen, E R Martin, R Schmidt, D Rujescu, L S Wang, J F Dartigues, R Mayeux, C Tzourio, A Hofman, M M Nöthen, C Graff, B M Psaty, L Jones, J L Haines, P A Holmans, M Lathrop, M A Pericak-Vance, L J Launer, L A Farrer, C M van Duijn, C Van Broeckhoven, V Moskvina, S Seshadri, J Williams, G D Schellenberg, P Amouyel
• Journal: Nature genetics (Nat Genet) Vol. 45 Issue 12 Pg. 1452-8 (Dec 2013) ISSN: 1546-1718 [Electronic] United States
• PMID: 24162737 (Publication Type: Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Topics

• Age of Onset
• Aged
• Aged, 80 and over
• Alzheimer Disease (epidemiology, genetics)
• Case-Control Studies
• Cohort Studies
• Female
• Genetic Loci
• Genetic Predisposition to Disease
• Genome-Wide Association Study (statistics & numerical data)
• Humans
• Male
• Middle Aged
• Polymorphism, Single Nucleotide