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

• Type of Material: Article
• Authors: L. C. Bidwell, University of Colorado at Boulder; J. E. McGeary, Rhode Island Hospital; J. C. Gray, University of Georgia; Rohan H. Palmer, Emory University; V. S. Knopik, Rhode Island Hospital; J. MacKillop, McMaster University
• Language: English
• Date: 2015-11-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.pbb.2015.09.018
• Title of Journal or Parent Work: Pharmacology Biochemistry and Behavior
• ISSN: 0091-3057
• Volume: 138
• Start Page: 104
• End Page: 110
• Grant/Funding Information: Funding was provided by the following grants: SAPRP 65626 from the Robert Wood Johnson Foundation and K23 AA016936 from NIH to James MacKillop; K23 DA033302 from NIDA to L. Cinnamon Bidwell; a Research Career Development Award from the Medical Research Service of the Department of Veteran Affairs, 1S10RR023457-01A1 and Shared equipment grants (ShEEP) from the Medical Research Service of the Department of Veteran Affairs to John McGeary; and K01 AA021113 from NIAAA to Rohan Palmer; and R01 DA023134 from NIDA to Valerie Knopik.; Dr. MacKillop is the holder of the Peter Boris Chair in Addictions Research, which partially supported his role.
• Keywords: Female; Middle Aged; Intermediate phenotype; Nicotine; Polymorphism, Single Nucleotide; Motives; Motivation; African Americans; Neuropsychological Tests; SNP; Smoking; African American; Young Adult; Genetic Variation; United States; Dopamine; Drug Tolerance; Humans; Adult; Craving; Male; Genotype; Haplotype
• Research Categories: Biology, Genetics; Psychology, Behavioral; Health Sciences, Mental Health

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.