The familial occurence of alcoholism has been known for many years. Approximatly 50-60% of individual differences in risk for alcoholism is genetic, and this proportion is approximately equal in man and woman. The goal of this article is to review the current status in the search for 'candidate genes' for alcohol dependence. There are three basic approaches to identifying important genes. First, one can target genes based on their presumed importance in influencing alcohol sensitivity. The targeted gene can be overexpressed, underexpressed, or disrupted to the extent that its functionis ablated (a gene knock-out). Second, one can seek genes that are identified as important because they are differentially expressed. Third, one can seek variations in the sequence of genes that are associated with alcohol sensitivity. The first approach can only be attempted using genetic animal models. Each approach will be reviewed, with an emphasis on the second and third. The examples of statistical measures will be present, the differences between family designed studies and association studies in compare to unrelated healthy volunteers will be discussed.
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