Genetic variation in the choline O-acetyltransferase gene in depression and Alzheimer's disease: the VITA and Milano studies.

Linkage studies point to the long arm of chromosome 10 being a susceptibility region for Alzheimer's disease (AD). Additionally, the gene choline O-acetyltransferase (CHAT) located on chromosome 10 was discussed for conveying risk towards AD, but the results are ambiguous. We examined a possible association of nineteen single-nucleotide polymorphisms (SNPs) in the CHAT gene in a longitudinal cohort study, the Vienna Tansdanube Aging (VITA)-study, in which all subjects were 75 years old at baseline. For replication, we used a more heterogeneous case-control sample from Milano with early and late AD. Nominal allelic and genotypic associations with AD risk in the cross-sectional VITA sample were found for rs3810950 (p = 0.038 for genotype, OR = 1.66 95% CI 1.03-2.68, p = 0.052 allele-wise). When combining both VITA- and Milano study rs3810950 was significantly associated with AD (p(combined) = 0.01634; power = 82%). This association was highly significant for APOEε4 carriers (p = 0.009 for genotype, OR = 3.21 95% CI 1.43-7.19 p = 0.007 allele-wise). Furthermore, an association of rs1880676 with AD was specific to carriers of the APOEε4 risk allele (p = 0.008, genotype; OR = 3.47 95% CI 1.50-8.01 p = 0.005 allele-wise). For depressive symptoms, we found a nominally significant association of rs3810950 with minor and major depression (p = 0.023, genotype; p = 0.008, allele). Applying Benjamini and Hochberg correction these associations could not be confirmed and also not be replicated in the more heterogeneous Milano sample. While our data therefore do not seem to support a major role for CHAT genetic variation in geriatric depression and AD, there might be a minor contribution in geriatric patients with depression and late onset AD, in particular those carrying the APOEε4 genotype.