Approach to the genetics of alcoholism: a review based on pathophysiology

Abstract

Alcohol dependence is a common disorder with a heterogenous etiology. The results of family, twin and adoption studies on alcoholism are reviewed. These studies have revealed a heritability of alcoholism of over 50%. After evaluating the results, it was epidemiologically stated that alcoholism is heterogenous complex disorder with a multiple genetic background. Modern molecular genetic techniques allow examining specific genes involved in the pathophysiology of complex diseases such as alcoholism. Strategies for gene identification are introduced to the reader, including family-based and association studies. The susceptibility genes that are in the focus of this article have been chosen because they are known to encode for underlying mechanisms that are linked to the pathophysiology of alcoholism or that are important for the pharmacotherapeutic approaches in the treatment of alcohol dependence. Postulated candidate genes of the metabolism of alcohol and of the involved neurotransmitter systems are introduced. Genetic studies on alcoholism examining the metabolism of alcohol and the dopaminergic, GABAergic, glutamatergic, opioid, cholinergic and serotonergic neurotransmitter systems as well as the neuropeptide Y are presented. The results are critically discussed followed by a discussion of possible consequences.