(Chen et al. 2012), and the effect of a functional CHRNA5 variant (rs16969968) on smoking quantity is reported to be stronger in early‐onset smokers than in late‐onset smokers (Hartz et al. 2012). Further, a genetic risk score composed of CHRNA5‐CHRNA3‐CHRNB4 and CYP2A6 (encoding the main metabolic enzyme for nicotine) variants highlighted in large CPD GWAS meta‐analyses (Liu et al. 2010; The Tobacco and Genetics Consortium 2010; Thorgeirsson et al. 2010) was unrelated to smoking initiation, but associated with progression to heavy smoking and ND (Belsky et al. 2013).
