Variants in the chromosome 15 cluster of genes encoding subunits of the nicotinic acetylcholine receptor, including CHRNA5/CHRNA3/CHRNB4, are among the most robustly replicated association signals for nicotine addiction. In addition, variants in CHRNA4 (encoding the α4 subunit of the neuronal nicotinic acetylcholine receptor) have also been suggested to influence various aspects of nicotine addiction,42, 43, 44 albeit inconsistently. A recent meta-analysis of linkage studies identified the CHRNA4 region on 20q13.2–q13.3 for maximum cigarettes smoked in a 24-h period. The DRD2/ANKK1 Taq1A allele, the subject of many studies on alcohol, has been studied in the context of nicotine addiction—a meta-analysis found support for an association for smoking initiation and current smoking but not for cigarettes/day.45
