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

Lambert, Jc; Ibrahim Verbaas CA,; Harold, D; Naj, Ac; Sims, R; Bellenguez, C; Jun, G; Destefano, Al; Bis, Jc; Beecham, Gw; Grenier Boley, B; Russo, G; Thornton Wells TA,; Jones, N; Smith, Av; Chouraki, V; Thomas, C; Ikram, Ma; Zelenika, D; Vardarajan, Bn; Kamatani, Y; Lin, Cf; Gerrish, A; Schmidt, H; Kunkle, B; Dunstan, Ml; Ruiz, A; Bihoreau, Mt; Choi, Sh; Reitz, C; Pasquier, F; Hollingworth, P; Ramirez, A; Hanon, O; Fitzpatrick, Al; Buxbaum, Jd; Campion, D; Crane, Pk; Baldwin, C; Becker, T; Gudnason, V; Cruchaga, C; Craig, D; Amin, N; Berr, C; Lopez, Ol; De Jager PL,; Deramecourt, V; Johnston, Ja; Evans, D; Lovestone, S; Letenneur, L; Morón, Fj; Rubinsztein, Dc; Eiriksdottir, G; Sleegers, K; Goate, Am; Fiévet, N; Huentelman, Mj; Gill, M; Brown, K; Kamboh, Mi; Keller, L; Barberger Gateau, P; Mcguinness, B; Larson, Eb; Green, R; Myers, Aj; Dufouil, C; Todd, S; Wallon, D; Love, S; Rogaeva, E; Gallacher, J; St George Hyslop, P; Clarimon, J; Lleo, A; Bayer, A; Tsuang, Dw; L, Yu; Tsolaki, M; Bossù, P; Spalletta, G; Proitsi, P; Collinge, J; Sorbi, S; Sanchez Garcia, F; Fox, Nc; Hardy, J; Naranjo, Mc; Bosco, P; Clarke, R; Brayne, C; Galimberti, D; Mancuso, M; Matthews, F; European Alzheimer's Disease Initiative,; Genetic,; Environmental Risk in Alzheimer's Disease,; Alzheimer's Disease Genetic Consortium,; Cohorts for Heart,; Aging Research in Genomic Epidemiology,; Moebus, S; Mecocci, P; DEL ZOMPO, Maria; Maier, W; Hampel, H; Pilotto, A; Bullido, M; Panza, F; Caffarra, P; Nacmias, B; Gilbert, Jr; Mayhaus, M; Lannfelt, L; Hakonarson, H; Pichler, S; Carrasquillo, Mm; Ingelsson, M; Beekly, D; Alvarez, V; Zou, F; Valladares, O; Younkin, Sg; Coto, E; Hamilton Nelson KL,; W, Gu; Razquin, C; Pastor, P; Mateo, I; Owen, Mj; Faber, Km; Jonsson, Pv; Combarros, O; O'Donovan, Mc; Cantwell, Lb; Soininen, H; Blacker, D; Mead, S; Mosley TH Jr,; Bennett, Da; Harris, Tb; Fratiglioni, L; Holmes, C; de Bruijn RF,; Passmore, P; Montine, Tj; Bettens, K; Rotter, Ji; Brice, A; Morgan, K; Foroud, Tm; Kukull, Wa; Hannequin, D; Powell, Jf; Nalls, Ma; Ritchie, K; Lunetta, Kl; Kauwe, Js; Boerwinkle, E; Riemenschneider, M; Boada, M; Hiltunen, M; Martin, Er; Schmidt, R; Rujescu, D; Wang, Ls; Dartigues, Jf; Mayeux, R; Tzourio, C; Hofman, A; Nöthen, Mm; Graff, C; Psaty, Bm; Jones, L; Haines, Jl; Holmans, Pa; Lathrop, M; Pericak Vance MA,; Launer, Lj; Farrer, La; van Duijn CM,; Van Broeckhoven, C; Moskvina, V; Seshadri, S; Williams, J; Schellenberg, Gd; Amouyel, P.

doi:10.1038/ng.2802

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.