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Pharmacol Biochem Behav. 2015 Nov;138:104-10. doi: 10.1016/j.pbb.2015.09.018. Epub 2015 Sep 26.

An initial investigation of associations between dopamine-linked genetic variation and smoking motives in African Americans.

Author information

1
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.
2
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.
3
Department of Psychology, 100 Hooper St., University of Georgia, Athens, GA 30602, United States.
4
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.
5
Peter Boris Centre for Addictions Research, McMaster University/St. Joseph's Healthcare Hamilton, 100 West 5th At., Hamilton, ON L8N 3K7, Canada.

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.

KEYWORDS:

African American; Dopamine; Haplotype; Intermediate phenotype; Motives; Nicotine; SNP

PMID:
26410615
PMCID:
PMC4635661
DOI:
10.1016/j.pbb.2015.09.018
[Indexed for MEDLINE]
Free PMC Article

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