The GWAS approach is beginning to uncover novel biology but will require further testing and confirmation, especially functional validation. We have attempted to present a new heuristic framework for GWAS of alcohol dependence, as one example of an approach for generating plausible functional hypotheses for candidate genes that may function within one or more stages of the addiction cycle. This heuristic framework could also be viewed as a reverse translational approach: information from a human genetic study used to guide functional genetic studies in animal models (see Table 3). For example, any one of the many well-validated animal models of alcohol-related phenotypes could be used to test the hypothesis that a candidate GWAS gene plays a specific role in a particular stage of the addiction cycle.
