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University of Virginia

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

Adam C Naj; Gyungah Jun; Gary W Beecham; Li-San Wang; Badri Narayan Vardarajan; Jacqueline Buros; Paul J Gallins; Joseph D Buxbaum; Gail P Jarvik; Paul K Crane; et al. (Profiled Authors: Mayeux, Richard; Bird, Thomas D; Haines, Jonathan L; Morris, John C; Goate, Alison M; Cairns, Nigel J; Hyman, Bradley T; Tanzi, Rudolph E; Growdon, John H; Farlow, Martin R; Hardy, John; Dickson, Dennis; Younkin, Steven G; Petersen, Ronald C; Sano, Mary; Bennett, David A; Cotman, Carl W; Cummings, Jeffrey L; Masliah, Eliezer; Galasko, Douglas; Miller, Bruce L; Pericak-Vance, Margaret A.; Gilbert, John R; Trojanowski, John Q; Schneider, Lon S; St George-Hyslop, Peter; DeKosky, Steven T; Schellenberg, Gerard D)

The John P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida, USA.
Nature genetics 2011;43(5):436-41.

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.

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