title: 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.
authors: School of Pedagogical and Educational Sciences, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
authors: Irene
authors: I
authors: Pappa
authors: School of Pedagogical and Educational Sciences, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
authors: Viara R
authors: VR
authors: Mileva-Seitz
authors: Centre for Child and Family Studies, Leiden University, Leiden, The Netherlands.
authors: Marian J
authors: MJ
authors: Bakermans-Kranenburg
authors: Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center-Sophia Children's Hospital, PO Box 2040, 3000 CA Rotterdam, The Netherlands; Department of Epidemiology, Erasmus University Medical Center-Sophia Children's Hospital, PO Box 2040, 3000 CA Rotterdam, The Netherlands; Department of Psychiatry, Erasmus University Medical Center-Sophia Children's Hospital, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors: Henning
authors: H
authors: Tiemeier
authors: School of Pedagogical and Educational Sciences, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands; Centre for Child and Family Studies, Leiden University, Leiden, The Netherlands. Electronic address: vanijzen@fsw.leidenuniv.nl.
authors: Marinus H
authors: MH
authors: van IJzendoorn
mesh_terms: D000293:Adolescent; D002648:Child; D002652:Child Behavior / Q000502:physiology*; D002657:Child Development / Q000502:physiology*; D056344:Executive Function / Q000502:physiology*; D006801:Humans; D000066553:Problem Behavior; D050638:Receptors, Dopamine D4 / Q000235:genetics*
chemical_list: C493599:DRD4 protein, human; D050638:Receptors, Dopamine D4
keywords: Behavioral phenotypes; Candidate gene; DRD4 exon III VNTR; Dopamine receptor D4; Genetic association