The 15q25 locus encodes the nicotinic acetylcholine receptor (nAChR) subunit α5, α3 and β4, members of the family of ligand-gated ion channels, which play an important role in the development of nicotine addiction (14,15). Nicotine binds to the nAChR causing its activation and the release of neurotransmitters. Variants on the 15q25 locus are associated with increased vulnerability to tobacco addiction, changed smoking behavior including increasing CPD (7,8,12,16), and were also identified as the main susceptibility locus in several lung cancer GWA studies (13,17,18). Some other loci associated with CPD identified through GWAS, including the CHRNB3 - CHRNA6 locus on 8p11, the CYP2A6 - CYP2B6 locus on 19q13 and the 7p14 locus, have also been found to be associated with a small increase in lung cancer risk (8).
