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.
Bibliographical noteFunding Information:
This research was supported by NIH grants P01 CA089392 from the National Cancer Institute , U01HG04422-02 from the National Human Genome Institute , R01DA026911 and K08DA030398 from the National Institute of Drug Abuse , K08DA030398 , KL2RR023249 by NIH/NCRR , and GA305231 from the Global Research Awards for Nicotine Dependence (GRAND) by Pfizer . Genotyping work at Perlegen Sciences was performed under NIDA Contract HHSN271200477471C. Phenotypic and genotypic data are stored in the NIDA Center for Genetic Studies (NCGS) at http://zork.wustl.edu/under NIDA Contract HHSN271200477451C (PIs J Tischfield and J Rice). Genotyping services were also provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University , contract number HHSN268200782096 . The funding organizations are not involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
- Case control study
- Genetic epidemiology
- Nicotine dependence
- Nicotinic receptor genes