Genetic variation in imprinted genes is associated with risk of late-onset Alzheimer's disease

J Alzheimers Dis. 2015;44(3):989-94. doi: 10.3233/JAD-142106.


Epigenetic changes including genomic imprinting may affect risk of late-onset Alzheimer's disease (LOAD). There are >100 known imprinted genes and most of them are expressed in human brain. In this study, we examined the association of single nucleotide polymorphisms (SNPs) in 93 imprinted genes with LOAD risk in 1291 LOAD cases and 958 cognitively normal controls. We performed single-site, gene-based, and haplotype analyses. Single-site analysis showed 14 significant associations at p < 0.01. The most significant SNP (rs11770199; p = 0.0003) in single-site analysis was located on chromosome 7 in the GRB10 gene. Gene-based analyses revealed four significant associations in the WT1, ZC3H12C, DLGAP2, and GPR1 genes at p < 0.05. The haplotype analysis also revealed significant associations with three genes (ZC3H12C, DLGAP2, and GPR1). These findings suggest a possible role of imprinted genes in AD pathogenesis that show specific expression in the brain.

Keywords: Brain; gene expression; imprinting; late onset Alzheimer's disease.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / genetics*
  • Female
  • GRB10 Adaptor Protein / genetics
  • Genetic Association Studies
  • Genetic Predisposition to Disease / genetics*
  • Genomic Imprinting / genetics*
  • Haplotypes
  • Humans
  • Male
  • Nerve Tissue Proteins / genetics
  • Polymorphism, Single Nucleotide / genetics*
  • Receptors, G-Protein-Coupled / genetics
  • Ribonucleases / genetics
  • Transcription Factors / genetics
  • WT1 Proteins / genetics


  • DLGAP2 protein, human
  • GPR1 protein, human
  • GRB10 protein, human
  • Nerve Tissue Proteins
  • Receptors, G-Protein-Coupled
  • Transcription Factors
  • WT1 Proteins
  • WT1 protein, human
  • GRB10 Adaptor Protein
  • Ribonucleases
  • ZC3H12A protein, human