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)).
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; 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; 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.. - In: NATURE GENETICS. - ISSN 1061-4036. - STAMPA. - 43(5):(2011), pp. 429-435. [10.1038/ng.803]
Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease.
NACMIAS, BENEDETTA;SORBI, SANDRO;
2011
Abstract
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)).
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