Alcoholism, which is defined by inability to stop drinking, drinking in the presence of
severe psychological and physiological issues, high tolerance and withdrawal symptoms, affects approximately 5 percent of the United States population, according to a 2007 article in the Journal "Addiction." Risk for alcoholism involves genetic and environmental factors that act both independently and together to produce this complex disease.
Family History Influences Alcoholism
Family history can provide clues to the underlying genetic risk of complex diseases
like alcoholism. Parents, siblings and children of alcoholics have a two to eight-fold higher risk of alcohol dependence than individuals without any first-degree relatives with alcoholism, according to a 1998 article in the "Archives of General Psychiatry." However, genetic studies on families have found that the transmission of alcoholism over generations is not solely due to growing up in the same household as an alcoholic. A 2004 twin study by Knopik et al. published in "Psychological Medicine" has shown that about 47 percent of the difference in risk of alcoholism is due to changes in genes or "genetic variants," while the remaining 53 percent of the difference in risk is due to environmental differences.
Multiple Genetic Variants Influence Alcoholism
Alcoholism is a genetically complex disease, which means that changes in several
different genes work together in the context of a vulnerable environment to produce
disease. A vulnerable environment may include: parental or peer alcohol consumption; depression or other mental health problems; and cultural attitudes toward alcohol consumption. When scientists look for genetic variants associated with alcoholism, they take into account that the impact of a single genetic variant may be very small, and that many different combinations of genetic variants may produce alcoholism in different individuals and different environments. In general, genetic variants found in multiple studies involving 1,000 or more subjects and ideally, among several racial or ethnic populations, are more likely to be truly associated with a complex disease than variants found once, in small studies or in only one racial or ethnic group.
Genes Associated with Alcoholism
Sensitivity to alcohol is known to be influenced by changes in genes that code for the enzymes that break down alcohol. The ALDH2 gene makes the alcohol-metabolizing enzyme acetylaldehyde dehydrogenase. A variant in this gene makes this enzyme unable to break down alcohol, leading to unpleasant toxicity symptoms such as nausea, flushing and rapid heartbeat. People with one copy of this genetic variant break down alcohol more slowly than those with two working copies. Having only one working copy of this gene is associated with milder toxicity symptoms and a somewhat lower likelihood of developing alcoholism. People with no working copies of this genetic variant break down alcohol at an extremely slow rate and experience more severe toxicity symptoms. Understandably, these individuals are much less likely to develop alcoholism than those with two working copies of the ALDH2 gene. Genetic changes in the ALDH2 gene are more common in the Asian population, where rates of alcoholism are low.
The GABRA2 gene, which encodes a neurotransmitter receptor involved in behavioral response to alcohol, has consistently been associated with alcohol dependence. The GABRA2 receptor is the target of benzodiazepines, a class of drugs used to treat symptoms of alcohol withdrawal.
The CHRM2 gene, which encodes an acetylcholine neurotransmitter receptor, has been found to be associated with both alcoholism and depression.
The changes in the ALDH2, GABRA2 and CHRM2 genes are just a few examples
of genes that have been found to be associated with alcoholism by multiple
researchers. Ongoing large genetic studies like the Collaborative Study on the
Genetics of Alcoholism will continue to discover and tease apart the complex relationship between genes, environmental exposures and alcoholism.
References
- "Proceedings of the National Academy of Science (PNAS);" A Genome-Wide Association Study of Alcohol Dependence; Laura J. Bierut, et al.; 2010.
- "Addiction;" The Alcohol Dependence Syndrome, 30 Years Later: a Commentary; Ting-Kai Li, et al.; 2007.
- "Archives of General Psychiatry;" Familial Transmission of Substance Dependence: Alcohol, Marijuana, Cocaine and Habitual Smoking: a Report From the Collaborative Study on the Genetics of Alcoholism; Laura Bierut, et al.; 1998.
- "Archives of General Psychiatry"; Familial Transmission of Substance Use Disorders; Kathleen Merikangas, et al.; 1998.
- "Psychological Medicine;" Genetic Effects on Alcohol Dependence Risk: Re-Evaluating the Importance of Psychiatric and Other Heritable Risk Factors. VS Knopik, et al.; 2004.
