Genetics of alcohol dependence.

Twin, family, and adoption studies have consistently shown that genetic factors play an important role in the pathogenesis of alcohol dependence. Numerous studies have aimed to identify genes that contribute to susceptibility to alcohol dependence. Whole-genome linkage studies have identified several chromosomal regions that are linked with alcohol dependence. Association studies have also identified genes associated with alcohol dependence. Alcohol-metabolizing enzymes, such as alcohol dehydrogenase-1B and aldehyde dehydrogenase-2, are the most well-established genes that have polymorphisms associated with the risk for alcohol dependence. Polymorphisms in gamma-aminobutyric acid receptor genes are also reported to be associated with alcohol dependence. The polymorphism of opioid receptor mu 1 gene is of interest because it alters the treatment effects of naltrexone. Several genes related to neural transmission have been reported to be associated with alcohol dependence, but results are inconsistent among studies. One reason for these inconsistent results is the great heterogeneity of alcohol dependence. Classifying alcohol dependence into homogeneous phenotypes is a good strategy to solve this problem. Recently, several genome-wide association studies have been reported. Genome-wide association studies enable hypothesis-free genome mapping of vulnerability-contributing genes and are expected to add data to identify genes associated with the susceptibility to alcohol dependence. Knowledge of the genetic basis of alcohol dependence is growing and leads to a better understanding of the biological mechanisms of addiction, which can help with strategies to prevent and treat this disease.