different developmental stages of alcohol dependence, (2) the development and application of computational techniques that model the cumulative and combinatorial effects of genes and environments in a systematic manner, (3) the incorporation of a consistent set of proximal (e.g., peers) and distal (e.g., residency location) environmental measures across genetic studies of alcohol and other drugs, and (4) the development of ontologies of alcohol dependencies that can facilitate the development of future studies and the interpretation of their findings. In the future, family-based whole-genome studies and animal studies may be the best approaches to understanding all of these mechanisms; family studies, because they are likely to include extreme cases of alcoholics with an ancestral history of alcohol problems and associated neuronal and genetic susceptibilities; animal studies, because selection and congenic experiments provide more than adequate control over genetic background effects, as well as epigenetic and environmental effects. The application of systems biology and GEM to neuronal and alcohol metabolism processes involved in alcohol related diseases will help to provide a better understanding of how individual parts of the liability to alcohol-related diseases work as a whole. Further, incorporating environmental measures will be a powerful method for better understanding the nature of
