title: An initial investigation of associations between dopamine-linked genetic variation and smoking motives in African Americans.
abstract: Nicotine dependence (ND) is a heterogeneous phenotype with complex genetic influences that may vary across ethnicities. The use of intermediate phenotypes may clarify genetic influences and reveal specific etiological pathways. Prior work in European Americans has found that the four Primary Dependence Motives (PDM) subscales (Automaticity, Craving, Loss of Control, and Tolerance) of the Wisconsin Inventory of Smoking Motives represent core features of nicotine dependence and are promising intermediate phenotypes for understanding genetic pathways to ND. However, no studies have examined PDM as an intermediate phenotype in African American smokers, an ethnic population that displays unique patterns of smoking and genetic variation. In the current study, 268 African American daily smokers completed a phenotypic assessment and provided a sample of DNA. Associations among haplotypes in the NCAM1-TTC12-ANKK1-DRD2 gene cluster, a dopamine-related gene region associated with ND, PDM intermediate phenotypes, and ND were examined. Dopamine-related genetic variation in the DBH and COMT genes was also considered on an exploratory basis. Mediational analysis was used to test the indirect pathway from genetic variation to smoking motives to nicotine dependence. NCAM1-TTC12-ANKK1-DRD2 region variation was significantly associated with the Automaticity subscale and, further, Automaticity significantly mediated associations among NCAM1-TTC12-ANKK1-DRD2 cluster variants and ND. DBH was also significantly associated with Automaticity, Craving, and Tolerance; Automaticity and Tolerance also served as mediators of the DBH-ND relationship. These results suggest that PDM, Automaticity in particular, may be a viable intermediate phenotype for understanding dopamine-related genetic influences on ND in African American smokers. Findings support a model in which putatively dopaminergic variants exert influence on ND through an effect on patterns of automatic routinized smoking.
authors.affiliation: Institute of Cognitive Science, University of Colorado at Boulder, Boulder, CO 80304, United States; Division of Behavioral Genetics, Rhode Island Hospital, 1 Hoppin St., Providence, RI 02903, United States; Department of Psychiatry and Human Behavior, Alpert Medical School, Brown University, Providence, RI 02903, United States. Electronic address: lcb@colorado.edu.
authors.forename: L C
authors.initials: LC
authors.lastname: Bidwell
authors.affiliation: Providence Veterans Affairs Medical Center, 830 Chalkstone Avenue, Building 35, Providence, RI 02908, United States; Division of Behavioral Genetics, Rhode Island Hospital, 1 Hoppin St., Providence, RI 02903, United States; Department of Psychiatry and Human Behavior, Alpert Medical School, Brown University, Providence, RI 02903, United States.
authors.forename: J E
authors.initials: JE
authors.lastname: McGeary
authors.affiliation: Department of Psychology, 100 Hooper St., University of Georgia, Athens, GA 30602, United States.
authors.forename: J C
authors.initials: JC
authors.lastname: Gray
authors.affiliation: Division of Behavioral Genetics, Rhode Island Hospital, 1 Hoppin St., Providence, RI 02903, United States; Department of Psychiatry and Human Behavior, Alpert Medical School, Brown University, Providence, RI 02903, United States.
authors.forename: R H C
authors.initials: RH
authors.lastname: Palmer
authors.affiliation: Division of Behavioral Genetics, Rhode Island Hospital, 1 Hoppin St., Providence, RI 02903, United States; Department of Psychiatry and Human Behavior, Alpert Medical School, Brown University, Providence, RI 02903, United States.
authors.forename: V S
authors.initials: VS
authors.lastname: Knopik
authors.affiliation: Peter Boris Centre for Addictions Research, McMaster University/St. Joseph's Healthcare Hamilton, 100 West 5th At., Hamilton, ON L8N 3K7, Canada.
authors.forename: J
authors.initials: J
authors.lastname: MacKillop
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics* / Q000523:psychology*; D066249:Craving; D004298:Dopamine / Q000235:genetics*; D004361:Drug Tolerance; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009042:Motivation / Q000235:genetics*; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000235:genetics* / Q000523:psychology*; D014481:United States; D055815:Young Adult
chemical_list: D004298:Dopamine
keywords: African American; Dopamine; Haplotype; Intermediate phenotype; Motives; Nicotine; SNP