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Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease

  • Author(s): Naj, AC
  • Jun, G
  • Beecham, GW
  • Wang, LS
  • 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
  • George-Hyslop, PS
  • 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, LW
  • Johnson, N
  • Karlawish, J
  • Karydas, A
  • Kaye, JA
  • Kim, R
  • et al.

Published Web Location

https://doi.org/10.1038/ng.801Creative Commons Attribution 4.0 International Public License
Abstract

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. © 2011 Nature America, Inc. All rights reserved.

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