The present analysis was undertaken to extend prior pharmacogenetics research on prospective smoking cessation beyond individual polymorphisms or single gene analyses. Using data from a placebo-controlled randomized clinical trial of bupropion for smoking cessation (20), we explored the associations of 1295 SNPs within 58 candidate gene regions in the dopamine system, including nAChRs and intracellular signaling proteins. A systems-based approach and analysis has many advantages over the evaluation of single functional polymorphisms and single candidate gene approaches. By taking a more expansive approach to SNP selection and gene selection, we hope to provide more complete coverage of the underlying genetic variation within a suspected etiologic system. This is accomplished in two ways. In addition to the inclusion of putative functional polymorphisms, we have included a set of SNPs to comprehensively capture the underlying genetic architecture within each candidate gene. Likewise, by broadening our selection of candidate genes to include multiple genes in a interconnected system, rather than simply focusing on single putatively interesting genes, we hope to provide a more complete picture of the impact of the entire system. This
