To explore this association further we also examined association of the variant coding for R336C substitution with several sub-phenotypes related to nicotine addiction and the health consequences of smoking (Table 2). In selecting the smoking phenotypes and smoking-related diseases to study we were guided by previously observed associations between the key variant in CHRNA5, rs1051730/rs16969968 and CPD, LC, PAD, COPD and upper aerodigestive tract cancers.12 In addition, we have observed association of rs1051730-A with AAAs in Iceland (odds ratio (OR)=1.19, P=0.009). As a subtype of ND we also include the heavy smoking index,29 a measure that combines two of the key questions on the FTND,20 SQ and the time to first cigarette after waking up, with a score of 4 or higher being considered high and comparable to an FTND score of ~6.30 For the smoking-related diseases we also considered the effect of the variant in early-onset cases separately (Materials and Methods).
