COMT genotype and cognitive ability: A longitudinal aging study

Dopaminergic neurotransmission in the pre-frontal cortex (PFC) contributes to individual cognitive differences in animals and humans. Catechol-O-methyltransferase (COMT) influences dopamine concentration in the PFC. Functional variation in the human COMT gene occurs at a single nucleotide polymorphism (SNP)--472G>A--that results in a valine (Val) to methionine (Met) amino acid substitution (Val158Met). The Met/Met form is less active resulting in higher dopamine concentrations and thus may enhance cognitive function. We applied repeated measures mixed general linear modelling over three waves between ages 64 and 68 years to optimise cognitive phenotype characterisation in a cohort of 473 community volunteers who had validated childhood IQ data. After adjusting for childhood IQ, wave of testing and specific test type, COMT Val158Met genotype polymorphism had a significant overall effect on cognition (F(2,935.7)=7.92, p