Genetic Research: Who Is at Risk for Alcoholism?

Article excerpt

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) was founded 40 years ago to help elucidate the biological underpinnings of alcohol dependence, including the potential contribution of genetic factors. Twin, adoption, and family studies conclusively demonstrated that genetic factors account for 50 to 60 percent of the variance in risk for developing alcoholism. Case-control studies and linkage analyses have helped identify DNA variants that contribute to increased risk, and the NIAAA-sponsored Collaborative Studies on Genetics of Alcoholism (COGA) has the expressed goal of identifying contributing genes using state-of-the-art genetic technologies. These efforts have ascertained several genes that may contribute to an increased risk of alcoholism, including certain variants encoding alcohol-metabolizing enzymes and neurotransmitter receptors. Genome-wide association studies allowing the analysis of millions of genetic markers located throughout the genome will enable discovery of further candidate genes. In addition to these human studies, genetic animal models of alcohol's effects and alcohol use have greatly advanced our understanding of the genetic basis of alcoholism, resulting in the identification of quantitative trait loci and allowing for targeted manipulation of candidate genes. Novel research approaches-for example, into epigenetic mechanisms of gene regulation-also are under way and undoubtedly will further clarify the genetic basis of alcoholism. KEY WORDS: Alcohol dependence; alcoholism; genetics and heredity; genetic theory of alcohol and other drug (AOD) use; genetic causes of AOD use, abuse and dependence (genetic AOD); genetic risk and protective factors; hereditary versus environmental factors; genetic mapping; Collaborative Studies on Genetics of Alcoholism; human studies; animal studies

Evidence from archeological artifacts indicates that fermented beverages existed as early as 10,000 B.C. The excessive consumption of alcohol, however, results in dangers to the health and well being of the drinker and those around him or her. Today, the World Health Organization estimates that alcohol causes 1.8 million deaths (3.2 percent of all deaths) worldwide and 58.3 million (4 percent of total) disabilityadjusted lifeyears (DALYs)1 lost to disease ( substance_ abuse/facts/alcohol/en/ index.html). In the United States, alcohol dependence (i.e., alcoholism) is a major health problem, affecting 4 to 5 percent of the population at any given time, with a lifetime prevalence of 12.5 percent (Hasin et al. 2007).

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) was founded 40 years ago to further understanding of the biological underpinnings of alcohol dependence. Early genetic studies were focused on delineating whether environmental factors, genetic factors, or both contributed to the risk for alcohol dependence. Once it was apparent that genetics did indeed play a role in alcohol dependence, NIAAA began to fund studies seeking to identify relevant genes. Since then, studies in humans and animals have used complementary approaches to understand the genetics of alcohol use and dependence. This overview summarizes the evidence supporting a role for genetic factors in alcoholism and describes how new genetic findings could affect our understanding of the causes and factors contributing to this debilitating disease and could potentially guide the development of improved treatments.

Evidence of a Genetic Contribution to Alcohol Dependence

Several study designs, including twin, family, and adoption studies, are used to determine whether relatively common diseases, such as alcohol dependence, are caused at least in part by genetic factors and to estimate the magnitude of the overall genetic contribution. Twin studies compare the similarity in disease status (i.e., concordance2) between identical (i.e., monozygotic) and fraternal (i.e., dizygotic) twins. …


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