In this study, the primary locus associated with nausea while attempting to quit smoking was the chr15q25 locus. This locus, which includes genes encoding the β4, α5, and α3 nicotinic receptor subunits (CHRNB4, CHRNA5, and CHRNA3), is the predominant locus associated with nicotine dependence (Amos et al, 2008; Hung et al, 2008; Thorgeirsson et al, 2008). Carriers of risk alleles at this locus are 30–40% more likely to become nicotine dependent. As with the response to varenicline, the significant LD in this region suggests that these associations are likely to overlap with those for nicotine dependence, and thus nausea experienced while quitting may be directly related to nicotine dependence. Smokers who are more dependent smoke more cigarettes per day and have a higher daily intake of nicotine. The link between the chr15q25 locus genes and nausea may be explained by tolerance, such that those with a greater daily intake of nicotine are more tolerant and therefore experience less nausea in response to a nicotinic partial agonist such as varenicline. Alternatively, incidence of nausea may be elevated in subjects with greater
