Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

Nat Genet. 2011 May;43(5):429-35. doi: 10.1038/ng.803. Epub 2011 Apr 3.

Abstract

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10(-5). We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10(-17); including ADGC data, meta P = 5.0 × 10(-21)) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10(-14); including ADGC data, meta P = 1.2 × 10(-16)) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10(-4); including ADGC data, meta P = 8.6 × 10(-9)), CD33 (GERAD+, P = 2.2 × 10(-4); including ADGC data, meta P = 1.6 × 10(-9)) and EPHA1 (GERAD+, P = 3.4 × 10(-4); including ADGC data, meta P = 6.0 × 10(-10)).

Publication types

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

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • Adaptor Proteins, Signal Transducing / genetics*
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / genetics*
  • Antigens, CD / genetics*
  • Antigens, Differentiation, Myelomonocytic / genetics*
  • Case-Control 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

  • ABCA7 protein, human
  • ATP-Binding Cassette Transporters
  • Adaptor Proteins, Signal Transducing
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD2-associated protein
  • CD33 protein, human
  • Cytoskeletal Proteins
  • MS4A4E protein, human
  • Membrane Proteins
  • Sialic Acid Binding Ig-like Lectin 3
  • Receptor, EphA1