Candidate gene association studies investigate single nucleotide polymorphisms (SNPs) and other variants (e.g., variable number tandem repeats) in genes suggested in linkage analysis (Hernandez and Blazer 2006), and/or those with strong biological plausibility. These studies can compare unrelated groups (case–control) or members of family units (family-based) and may be useful in identifying genes that play a minor role in nicotine dependence (Portugal and Gould 2008; Risch and Merikangas 1996). Until recently, most studies have focused on a few select candidate gene regions and it is possible that many of the loci that influence smoking behavior may lie outside those previously studied regions (Caporaso et al. 2009). Other limitations include false positive results (Sullivan et al. 2001), small sample sizes, differences in measures of smoking behavior, and differences in ethnic and environmental backgrounds (Caporaso et al. 2009; Portugal and Gould 2008).
