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., DeStafano AL., Bis JC., Beecham GW., Grenier-Boley B., Russo G., Thorton-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., 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 MW., Gill M., Brown K., Kamboh MI., Keller L., Barberger-Gateau P., McGuiness 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., Deniz Naranjo MC., Bosco P., Clarke R., Brayne C., Galimberti D., Mancuso M., Matthews F., European Alzheimer's Disease Initiative (EADI) None., Genetic and Environmental Risk in Alzheimer's Disease None., Alzheimer's Disease Genetic Consortium None., Cohorts for Heart and Aging Research in Genomic Epidemiology None., Moebus S., Mecocci P., Del Zompo M., Maier W., Hampel H., Pilotto A., Bullido M., Panza F., Caffarra P., Nacmias B., Gilbert JR., Mayhaus M., Lannefelt 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., 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., Hiltuenen 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.
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.