Abstract
Genetic variation in the catechol-O-methyltransferase gene (COMT) can influence cognitive function, and this effect may depend on developmental stage. Using a large representative British birth cohort, we investigated the effect of COMT on cognitive function (verbal and non-verbal) at ages 8 and 15 years taking into account the possible modifying effect of pubertal stage. Five functional COMT polymorphisms, rs6269, rs4818, rs4680, rs737865 and rs165599 were analysed. Associations between COMT polymorphisms and cognition were tested using regression and latent variable structural equation modelling (SEM). Before correction for multiple testing, COMT rs737865 showed association with reading comprehension, verbal ability and global cognition at age 15 years in pubescent boys only. Although there was some evidence for age- and sex-specific effects of the COMT rs737865 none remained significant after correction for multiple testing. Further studies are necessary in order to make firmer conclusions.
Highlights
Genetic variation in the catechol-O-methyltransferase (COMT) gene is likely to be important for phenotypes associated with function of the prefrontal cortex (PFC), such as cognition (Dickinson and Elvevag, 2009)
Neuroimaging studies confirm that the COMT Val158Met polymorphism affects human prefrontal cortical function, and as such is strongly associated with differences in neural process underlying cognitive output (Dennis et al, 2010; Mier et al, 2009)
After correcting for multiple testing, the present study failed to demonstrate a significant effect of the five COMT single nucleotide polymorphism (SNP) on cognition in boys and girls at ages 8 and 15 years, providing little evidence that COMT variation can have an effect on cognitive abilities in childhood and adolescence
Summary
Genetic variation in the catechol-O-methyltransferase (COMT) gene is likely to be important for phenotypes associated with function of the prefrontal cortex (PFC), such as cognition (Dickinson and Elvevag, 2009). Neuroimaging studies confirm that the COMT Val158Met (rs4680) polymorphism affects human prefrontal cortical function, and as such is strongly associated with differences in neural process underlying cognitive output (Dennis et al, 2010; Mier et al, 2009). These findings do not necessarily imply any change in cognition. Some studies have indicated that this association might be specific to developmental stage (Barnett et al, 2007; Dumontheil et al, 2011; Raz et al, 2011).
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