In these clinical trials, the adverse event most commonly reported in patients receiving varenicline (1 mg twice per day) was nausea (Gonzales et al, 2006; Jorenby et al, 2006; Oncken et al, 2006). Nausea was reported by 30% of individuals in the varenicline group (ranging from 28% to 35% across the three clinical trials) vs 10% in the bupropion group, and 9% in the placebo group. The incidence of nausea in the varenicline treatment group, and in all three treatment groups combined, was associated primarily with SNPs in the chromosome 15q25 locus (Table 5 and Supplementary Table 1). Among varenicline-treated patients, nausea was most significantly associated with rs555018 in the CHRNA5 gene (OR=1.62; 95% CI: 1.19–2.20) and rs1190449 in the CHRNG gene (OR=1.57; 95% CI: 1.18–2.08), while in the three treatment groups combined, the most significant association was with rs6495309 in the CHRNB4 gene (OR=0.50; 95% CI: 0.36–0.70; p=4.04E–05).
