reduce the impact of nicotine use and dependence. Both the OPRM1 A118G SNP and DAT1 VTNR polymorphism have been associated with nicotine initiation, use and dependence (Verhagen et al., 2012). Smoking also has been shown to alter availability of both DA D2 receptors and mu opioid receptors in the brain (Scott et al., 2007, Weerts et al., 2014). By excluding regular smokers, we reduced the possible impact of cigarette smoking on opioid and dopamine receptors, and downstream opioid and dopamine effects on alcohol sensitivity. Third, the current study adjusted for key biological variables such as sex and ancestral origin in our analyses. Importantly, the study of the intermediate phenotype of subjective alcohol response in populations that span the continuum of alcohol consumption patterns ranging from social drinkers to the chronic relapsing heavy drinker is consistent with NIH research domain criteria objectives (Ray et al., 2016, Litten et al., 2015). Such an approach is also supported by Bearden and Freimer (2006), since meaningful phenotypes should vary continuously in the general population (i.e. normal distribution). Examination of alcohol response across different populations is critical to our understanding of the strength of genetic associations with individual differences in alcohol response.
