Genetics of alcoholism and related end-organ damage

As we noted at the outset, the study of alcoholism and of its organ-specific complications is at a critical point. Familial-genetic investigations of alcoholism, in particular the large adoption studies, have revealed a new and more sophisticated clinical picture as reflected in the three-way familial classification. It is clear from these subtypes, which include discrete symptoms, allied psychiatric entities, and baseline personality differences, that not all alcoholics have the same disorder. In the design of future studies of alcoholism, whether familial-genetic or biochemical, it is essential that the subtypes of alcoholics be known and specified and that results be interpreted in that context. Clearly, twin studies are required that consider specifically the stability and heritability of diagnostic subtypes. The same suggestions obtain for the end-organ complications of alcoholism. There is abundant evidence that not all alcoholics are liable to the same organ-specific complications induced by their addiction. Reliable familial-genetic studies of how this variable liability operates seem imperative if the mounting evidence of specific biochemical mechanisms of disease is to have a proper context. In particular, familial-genetic studies of transketolase and of fatty acid ethyl ester synthase are needed. The latter enzyme is being studied in one sample of alcoholic families in the Alcohol Research Center at Washington University Medical School. Finally, with the spectacular advances in recombinant DNA technology and the existence of laboratories experienced in alcohol-related studies, the molecular investigation of alcoholism and of end-organ damage will expand dramatically in the near future. The list of cloned candidate loci will grow and RFLP-based linkage studies will follow. The uniting of genetics, pathophysiology, and gene mapping in the study of alcoholism and its sequelae has begun and is opening a new chapter in the history of these disorders.