The persistence of smoking can be attributed to multiple diverse causes. Chief among these are genetic risk factors contributing to smoking behavior (Li et al, 2003; Maes et al, 2004; Sullivan and Kendler, 1999; The Tobacco and Genetics Consortium, 2010). Genome-wide association studies (GWAS) have identified a primary genetic locus on chromosome 15q25 that increases the likelihood of nicotine dependence by 30–40% in individuals who carry common risk alleles (Amos et al, 2008; Hung et al, 2008; Thorgeirsson et al, 2008), as well as increasing the risk for several smoking-related diseases (Broderick et al, 2009; Landi et al, 2009; Pillai et al, 2009; Thorgeirsson et al, 2008). This locus includes three nicotinic receptor subunit genes (CHRNA5, CHRNB4, and CHRNA3), and a gene expressed in the lungs (IREB2), any (or several) of which may contain variants that contribute to nicotine dependence risk (DeMeo et al, 2009). Indeed, evidence points to the presence of multiple independent polymorphisms associated with nicotine dependence (Saccone et al, 2010a, 2010b). GWAS meta-analyses have identified four additional loci associated with nicotine dependence (The Tobacco and Genetics Consortium,
