title: Association of a duplicated repeat polymorphism in the 5'-untranslated region of the DRD4 gene with novelty seeking.
abstract: Novelty Seeking (NS) is a human personality trait in which impulsive, exploratory, and thrill-seeking behaviors are displayed. Dopaminergic genes have been prime candidates in the search for the genetic factors underlying NS because of the central role that dopamine plays in the brain's reward system. We have investigated whether there is an association between a polymorphic 120 base pairs (bp) repeat that is located in the 5'-untranslated region of the dopamine D4 receptor gene (DRD4) and NS. We genotyped four separate groups from psychiatric clinical studies for the repeat polymorphism. There were significant associations with NS in the groups of bipolar (P = 0.01) and alcoholic (P = 0.006) families containing 267 and 172 subjects, respectively. Subjects who were homozygous for the single-copy allele (SS genotype) had higher mean NS scores. This trend was also observed in the two other studies that contained unrelated subjects diagnosed with depression (N = 143 and N = 148) but the associations between DRD4 duplication genotype and NS were not significant in these groups. In the data combined from all four clinical groups those genotyped as SS had higher mean scores for all four NS subscales with significant associations for impulsivity (P = 0.0006), extravagance (P = 0.04), disorderliness (P = 0.02), and total NS (P = 0.0003). However, given the low frequency of the single-copy allele, this polymorphism would account for only a small proportion of the variance of NS in the population.
authors.affiliation: Department of Pathology, Christchurch School of Medicine and Health Sciences, PO Box 4345, Christchurch, New Zealand. geraldine.rogers@chmeds.ac.nz
authors.forename: Geraldine
authors.initials: G
authors.lastname: Rogers
authors.forename: Peter
authors.initials: P
authors.lastname: Joyce
authors.forename: Roger
authors.initials: R
authors.lastname: Mulder
authors.forename: Douglas
authors.initials: D
authors.lastname: Sellman
authors.forename: Allison
authors.initials: A
authors.lastname: Miller
authors.forename: Melanie
authors.initials: M
authors.lastname: Allington
authors.forename: Robin
authors.initials: R
authors.lastname: Olds
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Wells
authors.forename: Martin
authors.initials: M
authors.lastname: Kennedy
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics*; D000328:Adult; D000428:Alcohol Drinking / Q000235:genetics; D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics; D003866:Depressive Disorder / Q000188:drug therapy / Q000235:genetics; D005106:Exploratory Behavior / Q000502:physiology*; D005260:Female; D020440:Gene Duplication; D005838:Genotype; D006801:Humans; D008297:Male; D010375:Pedigree; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050638:Receptors, Dopamine D4; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; C493599:DRD4 protein, human; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4