Differences in Sensitivity to Environment Depending on Catechol-O-Methyltransferase (COMT) Gene? A Meta-analysis of Child and Adolescent Gene-by-Environment Studies

To date, several gene-by-environment (GxE) meta-analyses have been conducted to provide cumulative GxE evidence from previous inconsistent empirical studies; however, these meta-analyses have mainly focused on the serotonin transporter gene (5-HTTLPR). The present study aimed to conduct the first meta-analysis that tested whether and how an important dopaminergic genethe catechol-O-methyltransferase (COMT) gene contributed to differences in child and adolescent environmental sensitivity. A total of 22 studies with 20,528 participants involving in various developmental outcomes (e.g., externalizing problems, emotional problems, cognitive development and social behaviors) met the inclusion criteria. The pooled effect size of environment-outcome associations in the Met-allele carriers (r=0.11, 95% CI=[0.07, 0.15], p<.001) did not significantly differ from that in the Val/Val homozygotes (r=0.14, 95% CI=[0.08, 0.20], p<0.001) (Q(contrast) (1)=0.37, p=0.54). The aggregated Liptak-Stouffer Z-score that combined the p-values of the COMT-environment interaction yield a nonsignificant result (p=0.52). Moreover, outcome domain, sample age, ethnicity and assessment methods for the environment and the outcome did not moderate the effect sizes. Thus far, the COMT Val158Met polymorphism fails to explain the differences in sensitivity to environment. Future studies might incorporate more factors, such as polygenic effects of genetic pathways, epigenetics (EpiG) processing and sexual dimorphism, into the COMT-environment interaction equation.