Integrative genetic analysis of alcohol dependence using the GeneNetwork Web resources

Not long ago, the idea that alcoholism had a genetic basis-even in part-was highly controversial (Goodwin 1971, 1975). Over the past 35 years, however, the contribution of genetic factors has become conventional wisdom. This change to a large extent results from compelling experimental studies utilizing inbred and recombinant inbred (RI) strains of rats and mice (e.g., Crabbe et al. 1983; Crabbe 1983; McClearn 1972). Over the last decade, the focus of genetic research in the alcohol field has shifted away from epidemiological and statistical estimates of alcoholism heritability to molecular studies of single gene variants that have explanatory, predictive, and even therapeutic utility. Large-scale genetic studies such as the Collaborative Study on the Genetics of Alcoholism (COGA) have highlighted variations (i.e., polymorphisms) in numerous genes that are related to alcohol use, abuse, and risk of dependence (for a review, see Edenberg and Foroud 2006). And the list of candidate genes keeps growing. However, just compiling lists of such genes is not satisfying. What is needed is an in-depth understanding of how DNA variants cause differences in alcohol dependence, especially in the context of a myriad of environmental contributing factors, such as diet, stressors, and previous drinking history. This article summarizes some of the challenges associated with generating this understanding and presents a Web-based resource that may aid researchers in better understanding the mechanisms through which alcohol acts on the body and how different genes influence this process.