Candidate genes for novelty-seeking: a meta-analysis of association studies of DRD4 exon III and COMT Val158Met.

OBJECTIVE: Two widely studied genetic polymorphisms in the dopaminergic system [DRD4 exon III variable number of tandem repeat (VNTR) and COMT Val158Met] have been reported to be associated with novelty-seeking, but the results have been highly inconsistent. Therefore, a meta-analysis of the associations between these two polymorphisms and novelty-seeking was conducted.

PARTICIPANTS AND METHODS: For DRD4, 24 studies comprising 27 samples and including 4933 participants were selected. Genotype grouping, sex, mean age, ethnicity, and sample characteristics were examined as moderators. For COMT, nine studies comprising 13 samples and including 2633 participants were selected. Sex, mean age, ethnicity, and sample characteristics were included as moderators. We also tested for possible publication bias.

RESULTS: The significant association between the DRD4 polymorphism and novelty-seeking was supported, but no association was found between the COMT polymorphism and novelty-seeking. In addition, our findings revealed that sex and age both directly moderate the relationship between DRD4 and novelty-seeking. Meanwhile, ethnicity can interact with age, sex, and genotype grouping, and age and sex can interact with each other, to moderate the association between the DRD4 exon III VNTR polymorphism and novelty-seeking.

CONCLUSION: Our results provide evidence of association between the DRD4 exon III VNTR polymorphism and novelty-seeking, which is inconsistent with the results of previous meta-analysis. Furthermore, several direct and indirect moderators are also identified to explain contradictory results in the existing literature. However, our results regarding COMT are consistent with those of previous meta-analysis.