An important, unique feature of our sample is the definition of controls: smokers (> 100 cigarettes lifetime) who have never exhibited symptoms of dependence. Genetic associations from this study thus provide insight into the transition from smoking to nicotine dependence. This design also circumvents noise that may occur if the control group includes non-smoking (unexposed) but genetically vulnerable individuals. We expect our results to overlap with those from studies of alternative phenotypes such as cigarettes-per-day, but differences in genetic findings may reflect important differences in the phenotypes.
