Consistent with the nicotine dependence results, a lower metabolism metric was associated with an increased risk of smoking within 5 minutes after waking (Table 2, Figure 2). The continuous CYP2A6 metabolism metric had a trending effect in COGA (p=0.07) and a significant effect in COGEND (p=0.01). In secondary meta-analysis, slow metabolizers had a 57% increased odds (OR=1.57, 95% CI 1.13–2.18, p=0.007) of smoking within 5 minutes after waking compared to normal metabolizers (Table S2). The CYP2A6 metabolism metric was not associated with smoking more than 20 cigarettes per day in either sample or meta-analysis (Table 2, Figure 2). Secondary analyses examining the effect of the metabolism metric on smoking behaviors after controlling for DSM-IV alcohol dependence illustrates similar results (Table S3), supporting that the associations are not dependent on alcoholism status.
