Using a systems-based candidate gene approach we have identified polymorphisms within the β2 nicotinic acetylcholine receptor (CHRNB2) that exhibits significant association with the abstinence rates at EOT and at 6-month follow-up in a placebo-controlled trial of bupropion for smoking cessation. The association with abstinence was observed for two highly correlated (r2∼0.96) SNPs (rs2072661 and rs2072660) within the 3′UTR. Although the effects were independent of treatment, there was an indication of potential effect modification by bupropion. Specifically, although there was a difference in relapse rates at EOT between carriers and non-carriers for individuals who received bupropion, there was a substantial increase in relapse rates for those individuals carrying the minor allele after they went off treatment (Figure 2). Haplotype analysis capturing the genetic variability within the region confirmed the association across multiple SNPs and further indicated the independent role of the two SNPs. However, because of the high correlation between these SNPs, joint regression modeling was unable to discern the independent effect of each. Follow-up analyses on the top SNP (rs2072661) indicated a role in the time to relapse within the
