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Association of the Dopamine D4 Receptor (DRD4) Gene and Approach-Related Personality Traits: Meta-Analysis and New Data

      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.

      Key Words

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      • With Great Power Comes Great Responsibility: Meta-Analytic Proof for a Timeless Insight
        Biological PsychiatryVol. 69Issue 10
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          The last decade has seen an explosion in the number of studies relating polymorphisms in candidate genes to various behavioral and neural phenotypes. Reviews of the literature often report a plethora of questionable associations that could not be replicated or were even in the opposite direction in independent studies (1,2). Because of the high publication rate and the equally high rate of false positive findings and despite their inherent limitations, meta-analyses—like the one by Barnett et al.
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