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 (G×E) meta-analyses have been conducted to provide cumulative G×E 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 gene—the 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) (Qcontrast (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.
KeywordsMeta-analysis COMT Gene-by-environment interaction (G×E) Child Adolescent
We are grateful to the authors of included studies who generously provided statistical information for our data extraction. We thank Marian J. Bakermans-Kranenburg, Vrije Universiteit Amsterdam, and Huiyong Fan, Bohai University for their statistical assistance.
C.C. conceived of the study, participated in its design and data analysis and drafted the manuscript; L.C. participated in data analysis and interpretation of the data and helped to draft the manuscript; J.C. participated in the design and helped to draft the manuscript. All authors read and approved the final manuscript.
This study was supported by the National Natural Science Foundation of China (31800936), the Social Science Planning Fund of Shandong Province (18DJYJ01) and the Fundamental Research Funds of Shandong University (2018GN022) to C.C. L.C. was supported by the Social Science Planning Fund of Shandong Province (17CSZJ01).
Data Sharing and Declaration
The datasets generated and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
All research reported on in the manuscript was conducted in compliance with APA ethical principles. The study consisted of secondary analyses of de-identified data, and therefore did not require ethics board approval.
As the study was a quantitative synthesis of publicly available material, the informed consent from participants was not required.
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