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.

PORCELLINI E;LICASTRO F;
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)).
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
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/102949
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