title: Effects of dopamine receptor D4 variation on alcohol and tobacco use and on novelty seeking: multivariate linkage and association analysis.
abstract: The dopamine D4 receptor gene contains a polymorphic sequence consisting of a variable number of 48-base-pair (bp) repeats, and there have been a number of reports that this polymorphism is associated with variation in novelty seeking or in substance abuse and addictive behaviors. In this study we have assessed the linkage and association of DRD4 genotype with novelty seeking, alcohol use, and smoking in a sample of 377 dizygotic twin pairs and 15 single twins recruited from the Australian Twin Registry (ATR). We found no evidence of linkage or association of the DRD4 locus with any of the phenotypes. We made use of repeated measures for some phenotypes to increase power by multivariate genetic analysis, but allelic effects were still non-significant. Specifically, it has been suggested that the DRD4 7-repeat allele is associated with increased novelty seeking in males but we found no evidence for this, despite considerable power to do so. We conclude that DRD4 variation does not have an effect on use of alcohol and the problems that arise from it, on smoking, or on novelty seeking behavior.
authors.affiliation: Queensland Institute of Medical Research, Brisbane, Australia. michelLu@qimr.edu.au
authors.forename: Michelle
authors.initials: M
authors.lastname: Luciano
authors.forename: G
authors.initials: G
authors.lastname: Zhu
authors.forename: K M
authors.initials: KM
authors.lastname: Kirk
authors.forename: J B
authors.initials: JB
authors.lastname: Whitfield
authors.forename: R
authors.initials: R
authors.lastname: Butler
authors.forename: A C
authors.initials: AC
authors.lastname: Heath
authors.forename: P A F
authors.initials: PA
authors.lastname: Madden
authors.forename: N G
authors.initials: NG
authors.lastname: Martin
mesh_terms: D001315:Australia; D004327:Drinking Behavior; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D015999:Multivariate Analysis; D010641:Phenotype; D011110:Polymorphism, Genetic; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050638:Receptors, Dopamine D4; D012907:Smoking; D014427:Twins / Q000235:genetics / Q000706:statistics & numerical data; D014429:Twins, Dizygotic / Q000235:genetics / Q000706:statistics & numerical data; D014430:Twins, Monozygotic / Q000235:genetics / Q000706:statistics & numerical data
chemical_list: C493599:DRD4 protein, human; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4