The magnificent seven: A quantitative review of dopamine receptor d4 and its association with child behavior

Abstract

A large volume of behavioral research has explored the variable number of tandem repeat (VNTR) polymorphism on the dopamine receptor D4 gene (DRD4). However, findings are inconsistent and there is no agreement about what constitutes "functional" and "less functional" variants at this locus. First, we systematically review studies exploring biological differences between DRD4 VNTRs (k=21). Second, we systematically review studies relating DRD4 variation to behavioral traits in population-based, non-clinical samples of children and adolescents (k=46; N=13,195), highlighting the various genotypic classifications previously used. Third, we use meta-analyses to examine associations of DRD4 VNTRs with five broadly-defined behavioral outcomes (externalizing and attention problems, executive function, social/emotional development, and "reactive" temperament). We identify a significant association of "longer" DRD4 variants with lower levels of executive function and social/emotional development, but not independent of the choice of genotypic classification. We suggest that until the functionality of DRD4 VNTRs is established, researchers should report all genotypic classifications to ensure full transparency and allow for further meta-analytic work.

Keywords: Behavioral phenotypes; Candidate gene; DRD4 exon III VNTR; Dopamine receptor D4; Genetic association.