The analyses presented here suggest that genetic factors have a modest impact on initial sensitivity to alcohol, but are largely inconclusive with respect to underlying biology. This underscores the need for prospective assessments of large, diverse samples to clarify the biological mechanisms underlying alcohol sensitivity and how they may differ across ancestries. Prior evidence that low initial sensitivity is associated with later alcohol misuse (Barnett et al., 2014; Heath et al., 1999; Schuckit, 1994) suggests that SRE scores could be a useful risk indicator. Further elucidation of the biological processes impacting initial sensitivity is necessary, and could be accomplished in part by characterizing loci implicated in the current study in model systems to determine whether, and how, genetic manipulations effect ethanol sensitivity. Another avenue for potential research is the identification of specific environmental factors that account for the balance of phenotypic variance in SRE scores; examples may include diet, pubertal status, or psychological stressors with physiological consequences. While we understand a great deal about alcohol metabolism via alcohol dehydrogenases and other pathways (Lieber, 2005; Marshall and Chambers, 2005), the subjective
