Follow-up study of susceptibility loci for Alzheimer's disease and onset age identified by genome-wide association

J Alzheimers Dis. 2010;19(4):1169-75. doi: 10.3233/JAD-2010-1310.

Abstract

Replication of genetic association findings in independent studies represents an important validation tool in the search for susceptibility genes for complex diseases such as Alzheimer's disease (AD). In a well-characterized memory-clinic based study comprising 1078 unrelated AD patients and 652 control individuals, we set out to replicate previously reported genome-wide association of four novel risk SNPs with AD and onset age, with first stage p-values ranging from 0.001 to 0.000004. We obtained evidence for association between rs179943, an intronic SNP in ATXN1 at 6p22.3, and affection status (OR = 0.63 (95% CI = 0.44-0.90; nominal p = 0.01)). Overall, our data provided independent support for association of at least one chromosomal locus with AD and warranted a more in-depth investigation of these regions for possible underlying functional variants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Aged
  • Alzheimer Disease / genetics*
  • Chromosomes, Human, Pair 6 / genetics
  • DNA Replication / genetics
  • Dementia, Vascular / genetics
  • Female
  • Follow-Up Studies
  • Genetic Loci / genetics*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study / methods*
  • Genotype
  • Humans
  • Introns
  • Male
  • Middle Aged
  • Neurodegenerative Diseases / genetics
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide / genetics
  • Prospective Studies