Pathway-based association studies are a useful tool to study the associations of multiple genes within a neurobiological pathway or system that has strong biological plausibility for association with a phenotype. If amply powered, such studies can account for multiple variants in interacting or related genes and may help to validate the role of SNPs or genes in the etiology of a nicotine dependence phenotype (Conti et al. 2008; Saccone et al. 2007; Wang et al. 2007). Wang and Li identified several pathways (calcium, dopamine receptor, and cAMP-mediated signaling) containing genes associated with smoking behavior phenotypes, including initiation, dependence, and cessation. There is genetic overlap in the main pathways identified for smoking behavior phenotypes, but the genes associated with each phenotype within a pathway are different (Wang and Li 2010). Many pathways important in addiction to cocaine, alcohol, opioids overlap with those important in nicotine addiction or smoking cessation, including gap junction, LTP, and MAPK signaling (Li 2008). These findings suggest that some but not all of the mechanisms underlying nicotine dependence are common with other substances in addiction. There are
