Recent findings from large scale genetic studies demonstrate that specific genetic variants contribute to the development of nicotine dependence and this research brings unprecedented opportunities for further characterization of the genetic risk for nicotine dependence and comorbid disorders. Recent genome-wide association meta-analyses of large samples with European descent identify associations between smoking quantity (cigarettes per day) and multiple genetic variants. The most consistent genetic finding points to a locus in the CHRNA5-CHRNA3-CHRNB4 gene cluster on chromosome 15 (Liu et al., 2010; TAG, 2010; Thorgeirsson et al., 2010). Evidence shows that the genetic risk for nicotine dependence is influenced by at least two distinct biological mechanisms: receptor functional variation in CHRNA5 marked by rs16969968 and variability in CHRNA5 mRNA expression tagged by rs588765 (Bierut et al., 2008; Wang et al., 2009). Joint analysis of the uncorrelated Single Nucleotide Polymorphisms (SNPs) rs16969968 and rs588765 indicates that these two variants each exert independent influence on nicotine dependence vulnerability (Saccone et al., 2010).
