For our top SNP we were able to perform specific additional analyses motivated by prior knowledge to refine its potential mechanism of impact via time to relapse, withdrawal symptoms, and interaction effects with a key biologically relevant gene, CHRNA4. Having a detailed phenotypic information prospectively gathered from a randomized placebo-controlled trial was crucial for this further analysis. However, the collection of detailed information limited the original size of the study and thus we were unable to conclusively determine via statistical criteria SNP-treatment or SNP–SNP interactions, although effect estimates were suggestive in some instances. Although we included individuals from several ethnic groups for the investigation of population structure, we were unable to confirm our findings across all the self-identified ethnic groups because of the limited sample size for groups other than Caucasians.
