Common Variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 Are Associated With Late-Onset Alzheimer's Disease

Nat Genet. 2011 May;43(5):436-41. doi: 10.1038/ng.801. Epub 2011 Apr 3.

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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / genetics*
  • Antigens, CD / genetics*
  • Antigens, Differentiation, Myelomonocytic / genetics*
  • Cohort Studies
  • Cytoskeletal Proteins / genetics*
  • Databases, Genetic
  • Female
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genome-Wide Association Study
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Multigene Family
  • Polymorphism, Single Nucleotide
  • Receptor, EphA1 / genetics*
  • Sialic Acid Binding Ig-like Lectin 3

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD2-associated protein
  • CD33 protein, human
  • Cytoskeletal Proteins
  • Membrane Proteins
  • Sialic Acid Binding Ig-like Lectin 3
  • Receptor, EphA1

Grant support