Controls were defined as smokers (individuals who smoked at least 100 cigarettes lifetime), but who never had any symptoms of dependence (lifetime FTND=0). The threshold of 100 cigarettes smoked over the lifetime is commonly used and has been employed by several major surveys such as National Survey on Drug Use and Health. By selecting controls who smoked, we focused on those genetic effects that are specific to the development of nicotine dependence rather than smoking initiation. Subjects with an FTND score of 1, 2, or 3 were excluded from this study. This design was to create a comparison between active nicotine dependent cases and a clean control group without ANY symptoms of dependence (FTND=0). This contrast was created to maximize the power to detect differences in any genetic or environmental risks between cases and controls.
