Using data from the Collaborative Genetic Study of Nicotine Dependence (COGEND), we employed a comprehensive approach to examine the relationship between nicotine dependence, comorbid psychiatric disorders, and specific high priority genetic variants for nicotine dependence. Because of the evidence of multiple genetic factors that independently contribute to nicotine dependence in the chromosome 15 region, we used diplotypes of rs16969968 and rs588765 to represent the genetic risk in the CHRNA5-CHRNA3-CHRNB4 nicotinic receptor subunit gene cluster. In this paper we examined the following: (1) whether dependent smokers (as compared to non-dependent smokers) had increased risk for comorbid psychiatric disorders, (2) whether the diplotypes were associated with each comorbid disorder (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)) and whether the associations remained significant after controlling for nicotine dependence, (3) whether the genetic risk for nicotine dependence associated with the diplotypes of SNPs (rs16969968, rs588765) was moderated by comorbid psychiatric disorders, and (4) the statistical power to test the above hypotheses. The answers to
