Despite the above limitations, these results represent an important first effort to characterize the identified genetic risk associated with the CHRNA5-CHRNA3-CHRNB4 nicotinic receptor subunit gene cluster in the context of comorbid disorders given that nicotine dependence is highly comorbid with many other psychiatric disorders. The concept of common liability to addiction supported by twin studies suggests a substantial proportion of genetic factors account for a general vulnerability for all substance dependence. However, we found that variants in the CHRNA5-CHRNA3-CHRNB4 nicotinic receptor subunit gene cluster are specific risks for nicotine dependence, and not shared among comorbid psychiatric disorders. We also found that the risk associated with these genetic variants and comorbid disorders are additive and this genetic risk was not modified by comorbid psychiatric disorders such as major depressive disorder or alcohol dependence. Future association studies of a larger sample size using a novel phenotype definition capturing the common liability to addiction may help identify genetic variants responsible for multiple substance dependence.
