Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.
| Title | Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. |
| Publication Type | Journal Article |
| Year of Publication | 2013 |
| Authors | 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, Fievet, 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, Naranjo, MCDeniz, 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, 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 |
| Corporate Authors | European Alzheimer's Disease Initiative (EADI), Genetic and Environmental Risk in Alzheimer's Disease, Alzheimer's Disease Genetic Consortium, Cohorts for Heart and Aging Research in Genomic Epidemiology |
| Journal | Nat Genet |
| Volume | 45 |
| Issue | 12 |
| Pagination | 1452-8 |
| Date Published | 2013 Dec |
| ISSN | 1546-1718 |
| Keywords | Age of Onset, Aged, Aged, 80 and over, Alzheimer Disease, Case-Control Studies, Cohort Studies, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide |
| 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. |
| DOI | 10.1038/ng.2802 |
| Alternate Journal | Nat. Genet. |
| PubMed ID | 24162737 |
| PubMed Central ID | PMC3896259 |
| Grant List | MR/K013041/1 / / Medical Research Council / United Kingdom G0801306 / / Medical Research Council / United Kingdom U01 HG006375 / HG / NHGRI NIH HHS / United States MC_U123160657 / / Medical Research Council / United Kingdom R01 AG016495 / AG / NIA NIH HHS / United States P50 AG005131 / AG / NIA NIH HHS / United States U24 AG021886 / AG / NIA NIH HHS / United States K25 AG041906 / AG / NIA NIH HHS / United States MC_U123160651 / / Medical Research Council / United Kingdom U01 AG032984 / AG / NIA NIH HHS / United States MC_U105292687 / / Medical Research Council / United Kingdom P50 AG008702 / AG / NIA NIH HHS / United States / / Medical Research Council / United Kingdom U01 AG016976 / AG / NIA NIH HHS / United States P30 AG008051 / AG / NIA NIH HHS / United States R01 AG017917 / AG / NIA NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States MC_U137686857 / / Medical Research Council / United Kingdom G0902227 / / Medical Research Council / United Kingdom 089703 / / Wellcome Trust / United Kingdom R01 HL105756 / HL / NHLBI NIH HHS / United States P50 AG016573 / AG / NIA NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States R01 AG008122 / AG / NIA NIH HHS / United States P50 AG005134 / AG / NIA NIH HHS / United States R01 AG033193 / AG / NIA NIH HHS / United States R01 NS080820 / NS / NINDS NIH HHS / United States 164 / / Alzheimer's Society / United Kingdom G0601846 / / Medical Research Council / United Kingdom R01 AG041797 / AG / NIA NIH HHS / United States R01 AG041232 / AG / NIA NIH HHS / United States P50 AG005138 / AG / NIA NIH HHS / United States R01 AG037212 / AG / NIA NIH HHS / United States / / Arthritis Research UK / United Kingdom R01 AG023629 / AG / NIA NIH HHS / United States 095317 / / Wellcome Trust / United Kingdom 100140 / / Wellcome Trust / United Kingdom / / Wellcome Trust / United Kingdom MC_G1000734 / / Medical Research Council / United Kingdom U01 AG049505 / AG / NIA NIH HHS / United States |