Examples of other genes for alcohol dependence that have documented evidence of functional consequences at the molecular and/or behavioral levels are shown in Fig. 1 (genes in ovals) and listed in Table 2. For example, alcohol dependence is associated with a variant within neuropeptide Y (NPY) (Mottagui-Tabar et al., 2005). In a landmark study haplotype-driven NPY expression (including the variant associated with alcohol dependence) predicted brain responses to emotional and stress challenges and was inversely correlated with trait anxiety (Zhou et al., 2008). The results are consistent with the function of NPY as an anxiolytic peptide and suggests that the association with alcohol dependence may be functionally mediated by alterations in NPY gene expression that affect individual differences in stress reactivity and anxiety; individuals with NPY variants that result in low brain expression are more likely to have high anxiety that leave them vulnerable to excessive alcohol consumption, particularly in the binge-intoxication phase (Xu et al., 2013).
