Examination of the Involvement of Cholinergic-Associated Genes in Nicotine Behaviors in European and African Americans.
- Authors
- Melroy-Greif, Whitney E; Simonson, Matthew A; Corley, Robin P; Lutz, Sharon M; Hokanson, John E; Ehringer, Marissa A
- Year
- 2017
- Journal
- Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco
- PMID
- 27613895
- DOI
- 10.1093/ntr/ntw200
- PMCID
- PMC5868095
INTRODUCTION: Cigarette smoking is a physiologically harmful habit. Nicotinic acetylcholine receptors (nAChRs) are bound by nicotine and upregulated in response to chronic exposure to nicotine. It is known that upregulation of these receptors is not due to a change in mRNA of these genes, however, more precise details on the process are still uncertain, with several plausible hypotheses describing how nAChRs are upregulated. We have manually curated a set of genes believed to play a role in nicotine-induced nAChR upregulation. Here, we test the hypothesis that these genes are associated with and contribute risk for nicotine dependence (ND) and the number of cigarettes smoked per day (CPD). METHODS: Studies with genotypic data on European and African Americans (EAs and AAs, respectively) were collected and a gene-based test was run to test for an association between each gene and ND and CPD. RESULTS: Although several novel genes were associated with CPD and ND at P < 0.05 in EAs and AAs, these associations did not survive correction for multiple testing. Previous associations between CHRNA3, CHRNA5, CHRNB4 and CPD in EAs were replicated. CONCLUSIONS: Our hypothesis-driven approach avoided many of the limitations inherent in pathway analyses and provided nominal evidence for association between cholinergic-related genes and nicotine behaviors. IMPLICATIONS: We evaluated the evidence for association between a manually curated set of genes and nicotine behaviors in European and African Americans. Although no genes were associated after multiple testing correction, this study has several strengths: by manually curating a set of genes we circumvented the limitations inherent in many pathway analyses and tested several genes that had not yet been examined in a human genetic study; gene-based tests are a useful way to test for association with a set of genes; and these genes were collected based on literature review and conversations with experts, highlighting the importance of scientific collaboration.
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External
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|---|---|---|---|---|
| Commentary on Chenoweth et al.: Assessing response to interventions for smoking cessation in diverse populations. | Young KA et al. | — | 2022 | → |
| The Role of A Priori-Identified Addiction and Smoking Gene Sets in Smoking Behaviors. | Evans LM et al. | — | 2020 | → |
| ADGRL3 (LPHN3) variants predict substance use disorder. | Arcos-Burgos M et al. | — | 2019 | → |
| Novel Methodologies and the Need for Big Data in Nicotine and Tobacco Genetics Research. | David SP | — | 2017 | → |
| The genetic epidemiology of substance use disorder: A review. | Prom-Wormley EC et al. | — | 2017 | → |