Gender-specific effects of the catechol-O-methyltransferase Val108/158Met polymorphism on cognitive function in children

Objective: The study aimed to determine the cognitive effect of the Val(108)/(158)Met polymorphism in the catechol-O-methyltransferase ( COMT) gene in children before and during puberty. This polymorphism affects cognitive function in healthy adults and may contribute to risk for schizophrenia. Method: COMT genotype was determined for 8,707 children from the Avon Longitudinal Study of Parents and Children ( ALSPAC), a geographically defined general population cohort of children born between April 1, 1991, and Dec. 31, 1992, in the southwest of England. Fourteen measures of cognitive function-including working memory, verbal and motor inhibition, attentional control, and IQ-were assessed at ages 8 and 10 years. Any pubertal development at age 9 years was reported by parents. Effects of COMT genotype on cognition and interactions with gender and puberty were assessed using general linear models. Results: In boys, genotype significantly affected executive function and explained up to 10 points normal variation in verbal IQ. The effects on IQ were significantly greater in pubertal than in prepubertal boys. In girls, there were no significant effects of genotype on cognition. Conclusions: This common polymorphism may be one of the genes of small effect that contribute to normal variation in IQ. The gender-specific nature of the effect and its possible interaction with puberty may be relevant to both normal cognitive and brain development and to abnormal development in disorders such as schizophrenia.