title: Association of the dopamine D4 receptor (DRD4) gene and approach-related personality traits: meta-analysis and new data.
abstract: BACKGROUND
  Two variants in the dopamine D4 receptor (DRD4) gene have been reported to be associated with human approach-related traits such as novelty seeking and extraversion. However, the strength of evidence for this association remains uncertain.
  
  
  METHODS
  We conducted a meta-analysis of published studies of the association between the DRD4 gene variable number of tandem repeats (VNTR) and C-521T polymorphisms and human approach-related personality traits, including novelty seeking, extraversion, and impulsivity, restricted to adult samples recruited from nonpsychiatric populations, and extended on this literature by attempting to confirm any evidence of association in a replication sample (n = 309) selected for extreme scores on the extraversion subscale of the Eysenck Personality Questionnaire from a large (n = 40,090) population-based sample.
  
  
  RESULTS
  Our initial meta-analysis supported the association of the DRD4 C-521T polymorphism, but not the VNTR polymorphism, with approach-related traits. This conclusion was qualified by evidence of significant publication bias and the failure to detect association in a replication sample comprising individuals at the extremes of the trait distribution. The association of the C-521T polymorphism observed in our initial meta-analysis was robust to the inclusion of these new data, but our revised meta-analysis indicated that the association was present for measures of novelty seeking and impulsivity but not for measures of extraversion.
  
  
  CONCLUSIONS
  The DRD4 gene may be associated with measures of novelty seeking and impulsivity but not extraversion. The association of the C-521T variant with these measures, if genuine, may account for up to 3% of phenotypic variance.
authors.affiliation: Department of Experimental Psychology, University of Bristol, Bristol, United Kingdom. marcus.munafo@bristol.ac.uk
authors.forename: Marcus R
authors.initials: MR
authors.lastname: Munafò
authors.forename: Binnaz
authors.initials: B
authors.lastname: Yalcin
authors.forename: Saffron A
authors.initials: SA
authors.lastname: Willis-Owen
authors.forename: Jonathan
authors.initials: J
authors.lastname: Flint
mesh_terms: D000328:Adult; D016206:Databases, Bibliographic / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D010551:Personality / Q000235:genetics*; D011110:Polymorphism, Genetic; D050638:Receptors, Dopamine D4 / Q000235:genetics*
chemical_list: C493599:DRD4 protein, human; D050638:Receptors, Dopamine D4