.Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of Novelty Seeking

Research Laboratory, S. Herzog Memorial Hospital, Jerusalem, Israel.
Nature Genetics (Impact Factor: 29.35). 02/1996; 12(1):78-80. DOI: 10.1038/ng0196-78
Source: PubMed


Human personality traits which can be reliably measured by any of a number of rating scales, show a considerable heritable component. The tridimensional personality questionnaire (TPQ) is one such instrument and was designed by Cloninger to measure four distinct domains of temperament - Novelty Seeking, Harm Avoidance, Reward Dependence and Persistence-that are hypothesized to be based on distinct neurochemical and genetic substrates. Cloninger proposed that individual variations in the Novelty Seeking trait are mediated by genetic variability in dopamine transmission. Individuals who score higher than average on the TPQ Novelty Seeking scale are characterized as impulsive, exploratory, fickle, excitable, quick-tempered and extravagant, whereas those who score lower than average tend to be reflective, rigid, loyal, stoic, slow-tempered and frugal. We now show that higher than average Novelty Seeking test scores in a group of 124 unrelated Israeli subjects are significantly associated with a particular exonic polymorphism, the 7 repeat allele in the locus for the D4 dopamine receptor gene (D4DR). The association of high Novelty Seeking and the 7-repeat allele was independent of ethnicity, sex or age of the subjects. This work, together with the accompanying confirmations in this issue, provides the first replicated association between a specific genetic locus involved in neurotransmission and a normal personality trait.

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Available from: Robert H Belmaker, Dec 16, 2015
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    • " - ghari et al . , 1995 ) and possibly lower gene expression ( Schoots & Van Toll , 2003 ) . Behavioral research has conventionally fo - cused on the negative implications of this polymorphism . DRD4 7þ has been linked to attention - deficit disorder ( Far - aone & Mick , 2010 ; Rowe et al . , 1999 ) and novelty seeking ( Benjamin et al . , 1996 ; Ebstein et al . , 1996 ) . In addition to the genetic associations to behavior traits , DRD4 has been associated with differences in neurocognitive function as reflected by magnetic resonance imaging of re - gional brain activation patterns and connectivity patterns in the frontal cortex ( Gilsbach et al . , 2012 ) , an area critical for ex - ecutive control "
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    • "A genetic polymorphism associated with dopamine receptor D4 gene, DRD4 VNTR, is among the first candidate genes that molecular genetics research has shown to be related to approach-related traits and behaviors (Cloninger, Adolfsson, & Svrakic, 1996; Ebstein et al., 1996). We did not develop formal hypotheses on this genetic polymorphism because prior research has generated 4 Hardy–Weinberg Equilibrium tests were run for the sample broken down by age and gender. "
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    • "The 7-repeat allele is a known risk factor of ADHD (Wu et al., 2012) and children with ADHD are often characterized as being fearless and impulsive. " Long " DRD4 variants have also been associated with increased novelty seeking in healthy 3-years olds (Ebstein et al., 1996). Children with long DRD4 VNTRs who are at risk for ADHD might also exhibit a less fearful response to facing a stranger during a laboratory setting. "
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