Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease.

Hollingworth, P; Harold, D; Sims, R; Gerrish, A; Lambert, Jc; Carrasquillo, Mm; Abraham, R; Hamshere, Ml; Pahwa, Js; Moskvina, V; Dowzell, K; Jones, N; Stretton, A; Thomas, C; Richards, A; Ivanov, D; Widdowson, C; Chapman, J; Lovestone, S; Powell, J; Proitsi, P; Lupton, Mk; Brayne, C; Rubinsztein, Dc; Gill, M; Lawlor, B; Lynch, A; Brown, Ks; Passmore, Pa; Craig, D; Mcguinness, B; Todd, S; Holmes, C; Mann, D; Smith, Ad; Beaumont, H; Warden, D; Wilcock, G; Love, S; Kehoe, Pg; Hooper, Nm; Vardy, Er; Hardy, J; Mead, S; Fox, Nc; Rossor, M; Collinge, J; Maier, W; Jessen, F; Rüther, E; Schürmann, B; Heun, R; Kölsch, H; VAN DEN BUSSCHE, H; Heuser, I; Kornhuber, J; Wiltfang, J; Dichgans, M; Frölich, L; Hampel, H; Gallacher, J; Hüll, M; Rujescu, D; Giegling, I; Goate, Am; Kauwe, Js; 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, Kh; Klopp, N; Wichmann, He; Pankratz, Vs; Sando, Sb; Aasly, Jo; Barcikowska, M; Wszolek, Zk; Dickson, Dw; GRAFF-RADFORD, Nr; Petersen, Rc; ALZHEIMER'S DISEASE NEUROIMAGING INITIATIVE,; VAN DUIJN CM,; Breteler, Mm; Ikram, Ma; Destefano, Al; Fitzpatrick, Al; Lopez, O; Launer, Lj; Seshadri, S; Charge, Consortium; Berr, C; Campion, D; Epelbaum, J; Dartigues, Jf; Tzourio, C; Alpérovitch, A; Lathrop, M; Eadi1, Consortium; Feulner, Tm; Friedrich, P; Riehle, C; Krawczak, M; Schreiber, S; Mayhaus, M; Nicolhaus, S; Wagenpfeil, S; Steinberg, S; Stefansson, H; Stefansson, K; Snaedal, J; Björnsson, S; Jonsson, Pv; Chouraki, V; GENIER-BOLEY, B; Hiltunen, M; Soininen, H; Combarros, O; Zelenika, D; Delepine, M; Bullido, Mj; Pasquier, F; Mateo, I; FRANK-GARCIA, A; Porcellini, E; Hanon, O; Coto, E; Alvarez, V; Bosco, P; Siciliano, G; Mancuso, M; Panza, F; Solfrizzi, V; Nacmias, B; Sorbi, S; Bossù, P; Piccardi, P; Arosio, B; Annoni, G; Seripa, D; Pilotto, A; Scarpini, E; Galimberti, D; Brice, A; Hannequin, D; Licastro, F; Jones, L; Holmans, Pa; Jonsson, T; Riemenschneider, M; Morgan, K; Younkin, Sg; Owen, Mj; O'Donovan, M; Amouyel, P; Williams, J

doi:10.1038/ng.803

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10(-5). We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10(-17); including ADGC data, meta P = 5.0 × 10(-21)) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10(-14); including ADGC data, meta P = 1.2 × 10(-16)) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10(-4); including ADGC data, meta P = 8.6 × 10(-9)), CD33 (GERAD+, P = 2.2 × 10(-4); including ADGC data, meta P = 1.6 × 10(-9)) and EPHA1 (GERAD+, P = 3.4 × 10(-4); including ADGC data, meta P = 6.0 × 10(-10)).