Population and familial association between the D4 dopamine receptor gene and measures of novelty seeking

Twin and adoption studies suggest that 30 to 60% of the variance in many personality traits is due to inherited factors. However, there is little knowledge of the number or identity of the responsible genes, how they differ between individuals, or how their gene products interact with the developing brain and with environmental and experiential factors to generate the complex blend of attitudes and actions that comprise human temperament. In the accompanying paper, Ebstein et al. have found a population association between a long allele of polymorphic exert III repeat sequence of the D4 dopamine receptor gene (D4DR) and the normal personality trait of Novelty Seeking. The possibility of a causal relationship between D4DR and Novelty Seeking is further supported by studies showing that the number of exon III repeats can affect the binding of ligands to the receptor; that D4DR is expressed in limbic areas involved in cognition and emotion; that dopamine mediates exploratory behaviour in experimental animals; that the rewarding effects of amphetamines and cocaine are related to dopamine release; and that Novelty Seeking is low in dopamine-deficient patients with Parkinson's disease. We investigated the relationship between D4DR exon III sequence variants and personality test scores in a population of 315 mostly male siblings, other family members and individuals from the United States. The association between long alleles of exon III and personality traits related to Novelty Seeking was confirmed. Moreover, family studies showed that this association is the result of genetic transmission rather than of population stratification.