Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease

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 Europ...

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Authors: 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; Moron, FJ; Rubinsztein, DC; Eiriksdottir, G; Sleegers, K; Goate, AM; Fievet, 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; Bossu, P; Spalletta, G; Proitsi, P; Collinge, J; Sorbi, S; Sanchez-Garcia, F; Fox, NC; Hardy, J; Naranjo, MCD; Bosco, P; Clarke, R; Brayne, C; Galimberti, D; Mancuso, M; Matthews, F; 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; Lannfelt, L; Hakonarson, H; Pichler, S; Carrasquillo, MM; Ingelsson, M; Beekly, D; Alvarez, V; Zou, FG; 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, RFAG; 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, JSK; Boerwinkle, E; Riemenschneider, M; Boada, M; Hiltunen, M; Martin, ER; Schmidt, R; Rujescu, D; Wang, LS; Dartigues, JF; Mayeux, R; Tzourio, C; Hofman, A; Nothen, 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
Format: Article
Status:Published version
Publication date:2013
Country:España
Institution:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repository:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p9503
Online Access:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=9503
https://europepmc.org/article/MED/24162737
Access Level:Open access
Summary: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 x 10(-8)) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.

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