In conclusion, substance dependence has a major impact on public health, and smoking is a leading modifiable contributor to death worldwide, killing more than 5 million people annually (20). Common variation in the chromosome 8p11 region, which contains the α6 and β3 nicotinic receptor subunit genes, contributes to heaviness of smoking in European Americans and is associated with nicotine dependence in African Americans. General liability and substance-specific genetic risk variants are predicted to contribute to the development of dependence. However, our data suggest that the genetic variants tagged by rs13273442 in this region most likely represent a risk factor that is specific to nicotine dependence. This variant does not appear to be associated with a general liability to alcohol or other drug dependence, though the power is reduced to confidently rule out a risk for other substance dependence. Finally, our findings suggest that multiple variants contribute to the association between this region and nicotine dependence. This work represents important next steps to improve our understanding of the genetic factors that underlie addiction, which we hope will provide insights into how to reduce nicotine dependence and improve smoking cessation.
