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

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.