Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of novelty seeking

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.