Genetic variants in the choline acetyltransferase (ChAT) gene are modestly associated with normal cognitive function in the elderly

J. Mengel-From, K. Christensen, M. Thinggaard, M. Mcgue, L. Christiansen

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Genetic variants in the choline acetyltransferase (ChAT) gene have been suggested as risk factors for neurodegenerative Alzheimer's disease (AD). Here we tested the importance of genetic variants in the ChAT gene in normal cognitive function of elderly in a study sample of Danish twins and singletons (N = 2070). The ChAT rs3810950 A allele, which has been associated with increased risk for AD, was found to be associated with a decrease cognitive status evaluated by a five-component cognitive composite score [P = 0.03, regression coefficient -0.30, 95% confidence interval (CI) -0.57 to -0.02], and the rs3810950 and rs8178990 ancestral GC haplotype was also associated with better cross-sectional cognitive composite score (P = 0.04, regression coefficient 0.59, 95% CI 0.03 to 1.16). Growth curve model analyses applied to up to 10 years of follow-up data showed that the rs3810950 A allele was associated with a lower cognitive composite score and Mini Mental State Examination at the lowest age (73 years of age), and was lower in the whole interval 73-82 although the absolute difference became smaller with age. Stratification by the presence of the APOE ε4 allele showed that rs3810950 AG/non-APOE ε4 carriers and rs3810950 AA/APOE ε4 carriers were associated with a lower cognitive composite score in younger elderly 73-83 years of age, similar to previous reports of association with AD.

Original languageEnglish (US)
Pages (from-to)876-882
Number of pages7
JournalGenes, Brain and Behavior
Volume10
Issue number8
DOIs
StatePublished - Nov 1 2011

Keywords

  • Ageing
  • Alzheimer's
  • Cognitive function
  • Dementia
  • Genes
  • MMSE
  • Oldest old

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