Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease.
The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P(M)) = 1.7 × 10(-9), joint analysis P (P(J)) = 1.7 × 10(-9); stages 1, 2 and 3, P(M) = 8.2 × 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P(M) = 8.6 × 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P(M) = 6.0 × 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P(M) = 1.6 × 10(-9)). We also replicated previous associations at CR1 (rs6701713; P(M) = 4.6 × 10(-10), P(J) = 5.2 × 10(-11)), CLU (rs1532278; P(M) = 8.3 × 10(-8), P(J) = 1.9 × 10(-8)), BIN1 (rs7561528; P(M) = 4.0 × 10(-14), P(J) = 5.2 × 10(-14)) and PICALM (rs561655; P(M) = 7.0 × 10(-11), P(J) = 1.0 × 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility.
Naj, AC; Jun, G; Beecham, GW; Wang, L-S; Vardarajan, BN; Buros, J; Gallins, PJ; Buxbaum, JD; Jarvik, GP; Crane, PK; Larson, EB; Bird, TD; Boeve, BF; Graff-Radford, NR; De Jager, PL; Evans, D; Schneider, JA; Carrasquillo, MM; Ertekin-Taner, N; Younkin, SG; Cruchaga, C; Kauwe, JSK; Nowotny, P; Kramer, P; Hardy, J; Huentelman, MJ; Myers, AJ; Barmada, MM; Demirci, FY; Baldwin, CT; Green, RC; Rogaeva, E; St George-Hyslop, P; Arnold, SE; Barber, R; Beach, T; Bigio, EH; Bowen, JD; Boxer, A; Burke, JR; Cairns, NJ; Carlson, CS; Carney, RM; Carroll, SL; Chui, HC; Clark, DG; Corneveaux, J; Cotman, CW; Cummings, JL; DeCarli, C; DeKosky, ST; Diaz-Arrastia, R; Dick, M; Dickson, DW; Ellis, WG; Faber, KM; Fallon, KB; Farlow, MR; Ferris, S; Frosch, MP; Galasko, DR; Ganguli, M; Gearing, M; Geschwind, DH; Ghetti, B; Gilbert, JR; Gilman, S; Giordani, B; Glass, JD; Growdon, JH; Hamilton, RL; Harrell, LE; Head, E; Honig, LS; Hulette, CM; Hyman, BT; Jicha, GA; Jin, L-W; Johnson, N; Karlawish, J; Karydas, A; Kaye, JA; Kim, R; Koo, EH; Kowall, NW; Lah, JJ; Levey, AI; Lieberman, AP; Lopez, OL; Mack, WJ; Marson, DC; Martiniuk, F; Mash, DC; Masliah, E; McCormick, WC; McCurry, SM; McDavid, AN; McKee, AC; Mesulam, M; Miller, BL; Miller, CA; Miller, JW; Parisi, JE; Perl, DP; Peskind, E; Petersen, RC; Poon, WW; Quinn, JF; Rajbhandary, RA; Raskind, M; Reisberg, B; Ringman, JM; Roberson, ED; Rosenberg, RN; Sano, M; Schneider, LS; Seeley, W; Shelanski, ML; Slifer, MA; Smith, CD; Sonnen, JA; Spina, S; Stern, RA; Tanzi, RE; Trojanowski, JQ; Troncoso, JC; Van Deerlin, VM; Vinters, HV; Vonsattel, JP; Weintraub, S; Welsh-Bohmer, KA; Williamson, J; Woltjer, RL; Cantwell, LB; Dombroski, BA; Beekly, D; Lunetta, KL; Martin, ER; Kamboh, MI; Saykin, AJ; Reiman, EM; Bennett, DA; Morris, JC; Montine, TJ; Goate, AM; Blacker, D; Tsuang, DW; Hakonarson, H; Kukull, WA; Foroud, TM; Haines, JL; Mayeux, R; Pericak-Vance, MA; Farrer, LA; Schellenberg, GD
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