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;Yu L;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;Gu W;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.

2013-01-01

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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.