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04-03-2019 | Empirical Research

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

Auteurs: Cong Cao, Lili Cao, Jie Chen

Gepubliceerd in: Journal of Youth and Adolescence | Uitgave 4/2019

Abstract

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) (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.

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When separate effect sizes were reported for the Met/Met and Val/Met genotypes in the study, this meta-analysis firstly combined them into the effect size for the Met allele. Besides, few studies adopted a recessive genetic model where they reported effect sizes for the Val allele versus the Met/Met genotype. If this was the case, the effect sizes for the Val allele were assigned to those for the Val/Met and Val/Val respectively in order to include these studies in this meta-analysis. A supplementary meta-analysis excluding these recessive studies was also conducted. The G×E findings and moderator results remained non-significant, which was consistent with the current findings.

When a longitudinal study assessed environment at sample age <10, but assessed outcome at sample age >10, this study was coded into the mixed age group.

The non-Caucasian group mainly included East Asian and African populations in this meta-analysis and was relatively homogeneous in allele frequencies (Palmatier, Kang, & Kidd 1999); therefore the effect size in this group was aggregated and compared with that in Caucasian group.

*Studies included in the meta-analyses are indicated with an asterisk.

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Titel: Differences in Sensitivity to Environment Depending on Catechol-O-Methyltransferase (COMT) Gene? A Meta-analysis of Child and Adolescent Gene-by-Environment Studies
Auteurs: Cong Cao
Lili Cao
Jie Chen
Publicatiedatum: 04-03-2019
Uitgeverij: Springer US
Gepubliceerd in: Journal of Youth and Adolescence / Uitgave 4/2019
Print ISSN: 0047-2891
Elektronisch ISSN: 1573-6601
DOI: https://doi.org/10.1007/s10964-019-01004-3

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