Nicotine dependence and comorbid psychiatric disorders: examination of specific genetic variants in the CHRNA5-A3-B4 nicotinic receptor genes.
- Authors
- Chen, Li-Shiun; Xian, Hong; Grucza, Richard A; Saccone, Nancy L; Wang, Jen C; Johnson, Eric O; Breslau, Naomi; Hatsukami, Dorothy; Bierut, Laura J
- Year
- 2012
- Journal
- Drug and alcohol dependence
- PMID
- 22336398
- DOI
- 10.1016/j.drugalcdep.2012.01.014
- PMCID
- PMC3376673
BACKGROUND: The associations between nicotine dependence and specific variants in the nicotinic receptor CHRNA5-A3-B4 subunit genes are irrefutable with replications in many studies. The relationship between the newly identified genetic risk variants for nicotine dependence and comorbid psychiatric disorders is unclear. We examined whether these genetic variants were associated with comorbid disorders and whether comorbid psychiatric disorders modified the genetic risk of nicotine dependence. METHODS: In a case control study of nicotine dependence with 2032 subjects of European descent, we used logistic regression models to examine the pleiotropy and risk moderation. Comorbid disorders examined were alcohol dependence, cannabis dependence, major depressive disorder, panic attack, social phobia, posttraumatic stress disorder (PTSD), attention deficit hyperactivity disorder (ADHD), conduct disorder, and antisocial personality disorder (ASPD). RESULTS: Nicotine dependence was associated with every examined comorbid psychiatric disorders, with odds ratio varying from 1.75 to 3.33. No evidence supported the associations between the genetic variants and the comorbid disorders (pleiotropy). No evidence suggested that the risks for nicotine dependence associated with the genetic variants vary with comorbid psychiatric disorders in general, but the power was limited in detecting interactions. CONCLUSIONS: The genetic risks of nicotine dependence associated with the CHRNA5-A3-B4 subunit genes are specific, and not shared among commonly comorbid psychiatric disorders. The risks for nicotine dependence associated with these genetic variants are not modified by comorbid psychiatric disorders such as major depressive disorder or alcohol dependence. However, the power is an important limitation in studying the interplay of comorbidity and genetic variants.
Power and Required Sample Size in Testing of Pleiotropy and InteractionFigure 1a. Power of Testing Pleiotropy When Adjusting for Nicotine Dependence: Effect Size by Prevalence of Comorbid Disorder (Response Variable)Figure 1b. Power of Testing Interaction: Effect Size by Prevalence of Comorbid Disorder (Covariate)Figure 1c. Required Sample Size for Testing Pleiotropy with 80% Power: Effect Size by Prevalence of Comorbid Disorder (Response Variable)Figure 1d. Required Sample Size for Testing Interaction with 80% Power: Effect Size by Prevalence of Comorbid Disorder (Covariate)
No entities extracted from this document yet.
No uploaded files.
In this knowledge base
| Title | Year | PMID |
|---|---|---|
| Endophenotypes for Alcohol Use Disorder: An Update on the Field. | 2015 | 26236574 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Disruption of <i>chrna5</i> blunts aversion and adaptive transcriptomic responses to nicotine and alcohol. | Goel T et al. | — | 2026 | → |
| Multivariate Bayesian variable selection for multi-trait genetic fine mapping. | Canida T et al. | — | 2025 | → |
| Tobacco use, trauma exposure and PTSD: a systematic review. | Shevorykin A et al. | — | 2024 | → |
| [Comorbidity of posttraumatic stress disorder and addiction from a biopsychosocial perspective]. | Kapfhammer HP | — | 2022 | → |
| Endophenotypes for Alcohol Use Disorder: An Update on the Field. | Salvatore JE et al. | — | 2015 | → |
| Negative affective states and cognitive impairments in nicotine dependence. | Hall FS et al. | — | 2015 | → |
| Neuronal nicotinic acetylcholine receptors: common molecular substrates of nicotine and alcohol dependence. | Hendrickson LM et al. | — | 2013 | → |
| Relationship between attention deficit hyperactivity disorder and alcohol dependence: a genetic view. | Wang KS | — | 2013 | → |
| Smoking and psychopathology increasingly associated in recent birth cohorts. | Talati A et al. | — | 2013 | → |
| Variants in the 15q25 gene cluster are associated with risk for schizophrenia and bipolar disorder. | Jackson KJ et al. | — | 2013 | → |