Academic journal article Alcohol Research: Current Reviews

Assessing the Genetic Risk for Alcohol Use Disorders

Academic journal article Alcohol Research: Current Reviews

Assessing the Genetic Risk for Alcohol Use Disorders

Article excerpt

According to the World Health Organization (http://www.who. int/substance_abuse/facts/alcohol/ en/index.html), each year alcohol causes 2.5 million (3.8 percent of total) deaths and 69.4 million (4.5 percent of total) disability-adjusted life-years (DALYs) lost to disease worldwide. Alcohol dependence (alcoholism) also is a major health problem in the United States, affecting 4 to 5 percent of the population at any given time (Grant et al. 2004); its lifetime prevalence is 12.5 percent (Hasin et al. 2007). Initially, it was unclear whether environmental factors, genetic factors, or both contributed to the risk for alcohol dependence. Early studies clearly demonstrated that genes have a role in the risk for alcohol dependence; however, it also is clear that a substantial portion of the risk for alcoholism is not genetically determined and may result from other factors, such as the environment in which a person is raised or peer influences. In addition, gene-environment interactions exist that modify alcoholism risk (for more information, see the accompanying article by Dick and Kendler, pp. 318-324).

Ever since it has become clear that genetic factors influence the risk for alcoholism, researchers have sought to identify the genes involved. However, the complex nature of alcohol dependence and related disorders has slowed progress in identifying these genes. Thus, existing data suggest that each individual genetic element has only a small influence and that it will be necessary to identify the relevant gene networks to gain a greater understanding of the contribution of genetics to alcohol abuse and dependence (for more information on genetic and molecular networks of risk, see the article by Wolen and Miles, pp. 306-317).

Historically, two major approaches have been used to determine the magnitude of the overall genetic contribution to alcohol dependence in specific populations. The first approach was to compare the similarity (i.e., concordance) for alcohol dependence among identical (i.e., monozygotic) and fraternal (i.e., dizygotic) twins--that is, these studies assessed whether if one twin had alcohol dependence the other twin did so as well. If the risk for alcoholism, at least in part, results from genetic factors, one would expect monozygotic twins, who have identical genomes, to have a higher concordance rate for alcohol dependence than dizygotic twins, who on average only share one-half of their genomes. Studies indeed have shown higher concordance rates among monozygotic twins, confirming the presence of a genetic component in the risk for alcoholism. The second approach involved family studies to estimate the overall similarity among family members sharing differing proportions of their genome (e.g., comparing sons with fathers or grandfathers). Together, these family and twin studies provided convergent evidence that genetic factors account for 50 to 60 percent of the total variance in the risk for alcohol dependence (Heath et al. 1997; McGue 1999).

On the basis of these findings, the next step was to identify specific genes that could influence the risk for alcoholism. Over the past three decades, new developments have made it possible to search for specific genes that influence the risk for alcohol dependence, both in human populations and in animal models. This article summarizes some of these approaches used in human populations and in studies of animal models. It also describes newer approaches aimed at analyzing the genetic basis of alcoholism at the level of the entire genome, thus moving beyond analyses of the roles of individual genes in the development of this devastating disease.

Identifying Genes Contributing to the Risk for Alcoholism

Approaches in Human Populations

In human studies, several strategies have been used to search for the genes that influence complex traits such as alcohol dependence, which are influenced by multiple genes with smaller effects rather than by one or more genes with larger effect sizes (Edenberg and Foroud 2006; also see the article by Agrawal and Bierut, pp. …

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