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Nat Genet. 2013 Dec;45(12):1452-8. doi: 10.1038/ng.2802. Epub 2013 Oct 27.

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); Genetic and Environmental Risk in Alzheimer's Disease; Alzheimer's Disease Genetic Consortium; Cohorts for Heart and Aging Research in Genomic Epidemiology, 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 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, 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.

Collaborators (268)

Alpérovitch A, Boland A, Delépoine M, Dubois B, Duron E, Epelbaum J, Van Cauwenberghe C, Engelborghs S, Vandenberghe R, De Deyn PP, Ferri R, Romano C, Caltagirone C, Orfei MD, Ciaramella A, Scarpini E, Fenoglio C, Siciliano G, Bonuccelli U, Bagnoli S, Bracco L, Bessi V, Cecchetti R, Bastgiani P, Squassina A, Seripa D, Frank-García A, Sastre I, Blesa R, Alcolea D, Suárez-Clavet M, Sánchez-Juan P, Muñoz Fernandez C, Aladro Benito Y, Thonberg H, Forshell C, Lilus L, Kinhult-Ståhlbom A, Giedraitis V, Kilander L, Brundin RM, Concari L, Helisalmi S, Koivisto AM, Haapasalo A, Solfrizzi V, Frisardi V, Ott J, Carney RM, Mash DC, Albert MS, Albin RL, Apostolova LG, Arnold SE, Barmada MM, Barnes LL, Beach TG, Bigio EH, Bird TD, Boeve BF, Bowen JD, Boxer A, Burk JR, Cairns NJ, Cao C, Carlson CS, Carroll SL, Chibnik LB, Chui HC, Clark DG, Corneveaux J, Cribbs DG, DeCarli C, DeKosky ST, Demirci FY, Dick M, Dickson DW, Duara R, Ertekin-Taner N, Fallon KB, Farlow MR, Ferris S, Frosch MP, Galasko GR, Ganguli M, Gearing M, Geschwind DH, Ghetti B, Gilman S, Glass JD, Growdon JH, Hamilton RL, Harrell LE, Head E, Honig LS, Hulette CM, Hyman BT, Jarvik GP, Jicha GA, Jin LW, Karydas A, Kauwe JS, Kaye JA, Kim R, Koo EH, Kowall NW, Kramer JH, Kramer P, LaFerla FM, Lah JJ, Levernez JB, Levey AI, Li G, Lieberman AP, Lyketsos CG, Mack WJ, Marson DC, Martiniuk F, Masliah E, McCormick WC, McCurry SM, McDavid AN, McKee AC, Mesulam M, Miller BL, Miller CA, Miller JW, Morris JC, Murrell JR, Olichney JM, Pankratz VS, Parasi JE, Peskind E, Peterson RC, Pierce A, Poon WW, Potter H, Quinn JF, Raj A, Raskind M, Raiman EM, Reisberg B, Ringman JM, Roberson ED, Rosen HJ, Rosenberg RN, Sano M, Saykin AJ, Schneider JA, Schneider LS, Seely WW, Smith AG, Sonnen JA, Spina S, Stern RA, Tanzi RE, Trojanowski JQ, Troncoso JC, Van Deerlin VM, Van Eldik LJ, Vinters HV, Vonsattel JP, Weintraub S, Welsh-Bohmer KA, Williamson J, Woltjer RL, Yu CE, Barber R, Au R, Wolf PA, Beiser A, Debette S, Yang Q, Weinstein G, Johnson AD, Wang J, Uitterlinden AG, Rivadeneira F, Koudstgaal PJ, Longstreth WT Jr, Becker JT, Kuller LH, Lumley T, Rice K, Garcia M, Aspelund T, Marksteiner JJ, Dal-Bianco P, Töglhofer AM, Freudenberger P, Ransmayr G, Benke T, Toeglhofer AM, Bressler J, Breteler MM, Fornage M, Hernández I, Rosende Roca M, Ana Mauleón M, Alegrat M, RamÍrez-Lorca R, González-Perez A, Chapman J, Stretton A, Morgan A, Kehoe PG, Medway C, Lord J, Turton J, Hooper NM, Vardy E, Warren JD, Schott JM, Uphill J, Ryan N, Rossor M, Ben-Shlomo Y, Makrina D, Gkatzima O, Lupton M, Koutroumani M, Avramidou D, Germanou A, Jessen F, Riedel-Heller S, Dichgans M, Heun R, Kölsch H, Schürmann B, Herold C, Lacour A, Drichel D, Hoffman P, Kornhuber J, Gu W, Feulner T, van den Bussche H, Lawlor B, Lynch A, Mann D, Smith AD, Warden D, Wilcock G, Heuser I, Wiltgang J, Frölich L, Hüll M, Mayo K, Livingston G, Bass NJ, Gurling H, McQuillen A, Gwilliam R, Deloukas P, Al-Chalabi A, Shaw CE, Singleton AB, Guerreiro R, Jöckel KH, Klopp N, Wichmann HE, Dickson DW, Graff-Radford NR, Ma L, Bisceglio G, Fisher E, Warner N, Pickering-Brown S.

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.

PMID:
24162737
[PubMed - indexed for MEDLINE]
PMCID:
PMC3896259
Free PMC Article

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