To date, the most compelling evidence for genetic risk variants contributing to nicotine dependence comes from a series of studies that have examined smoking behaviors and nicotine dependence across numerous populations. These genetic studies implicate variants in the chromosome 15q24-25 region in the development of heavy smoking and nicotine dependence, and this region includes the α5-α3-β4 nicotinic receptor gene cluster. This finding was first reported in a study that compared nicotine dependent cases to light smokers who had no symptoms of dependence, which focused the genetic study on the transition from regular smoking to dependence [12]. This genetic association, a correlation between genetic variants and nicotine dependence, is marked by multiple SNPs, including rs16969968 in the α5 cholinergic nicotinic receptor subunit gene CHRNA5. Individuals who have one copy of the risk variant have a 1.3 fold increase in developing nicotine dependence once exposed to smoking, and those with two copies of the risk variant have almost a two-fold increase in risk [13].
