Our results suggest that time to first cigarette after waking is a critical contributor to the association between the CYP2A6 metabolism metric and development of nicotine dependence assessed by the FTND criteria among daily smokers. Little consensus exists on the best measure of nicotine dependence, but research supports that two items from the FTND score, time to first cigarette after waking and cigarettes smoked per day, are strong, valid, reliable predictors of quitting behaviors, which are key indicators of dependence (Baker et al., 2007; Borland et al., 2010; Hyland et al., 2006). Studies also suggest that these two measures are distinct predictors of addiction (Borland et al., 2010; Lessov et al., 2004), chronic obstructive pulmonary disease (Guertin et al., 2015), and lung cancer (Gu et al., 2014), suggesting the possibility that different genetic factors may contribute to urgency to smoke and levels of cigarette consumption. In a sample of over 1000 young adults, Haberstick et al. (2007) found that time to first cigarette was the most informative measure of heritable factors from the FTND score. Our results complement these findings
