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Volume 19, Number 4, December 2008

photo of Fulton Crews, PhD
Dr. Fulton T. Crews
Director, Bowles Center for Alcohol Studies

The genetics of alcoholism is one of the great challenges of 21st century medicine. We know that alcoholism is associated with families. Genetics are important, although family association likely includes both genetic and environmental factors, since alcohol exposure differs in families with alcoholism. Both protective and risk genes are likely very important in the genetics of alcoholism. We know genes that metabolize alcohol play a role in the genetics of alcoholism. Individuals who have very fast alcohol dehydrogenase and/or slow aldehyde dehydrogenase gene alleles have an endogenous Antabuse®-like reaction to alcohol that protects them from becoming alcoholic. The endogenous Antabuse®-like reaction makes them sick when they drink alcohol, yet these metabolic alleles do not protect all from becoming alcoholics.
Many factors, including animal genetic models of alcoholism, suggest genes that regulate brain function may be important in alcoholism. Family history and risk for alcoholism are genetically linked to a low sedative response to alcohol. We don’t know which genes. The sedative response to alcohol is likely due to differences in the brain. There is a lot of effort to understand the sedative response, alcohol tolerance and physical dependence, but it is complicated and not well understood.
Likely equally important, not every alcoholic is the same. They have various alleles of about 20,000 genes, some of which are silenced depending upon if they came from the mother or father. Environmental factors, including nutrition, nurture, and all that shapes our development, make each human unique. Mental disease phenotypes that characterize a disease can include differences in tolerance, withdrawal, compulsive drive, impulsive actions promoting negative consequences, anti-social and social anxiety factors that contribute to the diagnosis of alcohol dependence. Another part of the complexity is that other mental diseases, such as depression and anxiety, are often diagnosed as co-morbid when combined with alcohol dependence. All of these factors make it very difficult for geneticists to find which alleles of genes associate with alcoholism.
What is exciting about Kirk Wilhelmsen’s work is the use of novel combinations of genes, unique environmental – gene associations and specific phenotypic aspects of the diagnosis that associates individuals with similar symptoms and allelic genotypes. This novel and interesting new direction requires incredible computing and mathematics but may unravel the tremendous complexity within the thousands of alleles of genes and different ways the brain drives our activity.