We aimed for the densest coverage of any genotyping array for the chr15q25.1 nicotinic acetylcholine receptor (nAChR) gene cluster (CHRNA5, CHRNA3 and CHRNB4), and the chr19q13.2 nicotine metabolizing enzyme genes (CYP2A6 and CYP2B6). The CYP2A6 gene plays a major role in the nicotine metabolism pathway [80, 81] while genes encoding for CYP isozymes, such as the CYP2B6 gene, may play a smaller role in influencing nicotine metabolism [82, 83]. An individual’s nicotine metabolism affects the level of circulating and sequestered nicotine and thus, nicotine intake [40, 84]. Nicotine binds to nAChRs, triggering neurotransmitter release and leads over time to nicotine dependence. nAChR activity, and thus nicotine dependence, is regulated by the cholinergic genes on chromosomes 8p11.21, 15q25.1 and 20q13.33 [16, 17, 21, 85–88].
