Twin studies have demonstrated that the amount of alcohol one consumes has a genetic influence [5]. Age at first drink appears to be associated with alcohol-related problem behavior, but progression to alcoholism is under stronger genetic control than initiation, and the effect of early exposure to predict outcome is genetically mediated [6]. Alcohol-related phenotypes are typical quantitative traits, with population variation attributable to multiple segregating loci with effects that are sensitive to environmental exposures. Given that many loci are likely to affect alcohol drinking behavior and the development of dependence, we need to shift our focus from a 'one gene at a time' approach to genetic networks. This can be done by considering the effects of molecular polymorphisms on phenotypes mediated via complex networks of transcriptional, protein, metabolic and neurogenetic endophenotypes. Here, we review genetic risk factors and transcriptional correlates for alcohol consumption in humans, with insights from studies on model genetic organisms.
