Alcoholism Risk Linked To Gene Involved In Brain Chemistry

The gene identified, GABRA2, is one of several genes that produce parts of the receptor for the brain's primary inhibitory neurotransmitter, GABA. GABA is a chemical messenger that carries information between nerve cells; when GABA binds to the GABA-receptors on a nerve cell, it inhibits the firing of that cell. GABA is known to be involved with some of the body's responses to alcohol consumption, such as loss of physical coordination, effect on mood, and alcohol withdrawal symptoms.

Alcoholism, which affects nearly 14 million Americans and can cause many social and health problems costing society an estimated $185 billion annually, is what scientists call a "complex" disease, meaning that many genes as well as environmental factors play a role in whether a person develops the disease.

While there is not one single "gene that causes alcoholism" the statistical link between this gene and the risk for alcoholism is powerful, said Howard J. Edenberg, Ph.D., Chancellor's Professor at the IU School of Medicine. Edenberg was the lead researcher for the study, which appears in the April issue of the American Journal of Human Genetics.

"Statistically, this is very strong evidence that this gene affects the risk of alcoholism," said Edenberg, professor of biochemistry and molecular biology and of medical and molecular genetics.

As researchers identify genes and brain signaling pathways associated with alcoholism -- and learn how they vary from one person to another -- opportunities should arise for development of more precisely targeted drugs, and for individualized approaches to prevent and treat alcoholism, Edenberg said.

"We may be able to target therapies and preventative treatments based on individual characteristics," he said. The research was done as part of the Collaborative Study on the Genetics of Alcoholism, a 15-year-old project that involves scientists at nine institutions across the country and is funded by the National Institute on Alcohol Abuse and Alcoholism, part of the National Institutes of Health.

The research team's analysis involved 2282 individuals from 262 families selected for study because they contained at least three alcoholic members. Earlier genetic analyses by this team implicated a particular section of chromosome 4 as affecting both the risk for alcoholism and certain types of brainwave patterns that have been linked to alcoholics. Within that region are genes that make proteins enabling GABA to signal to nerve cells and so do its work in the brain.

The researchers analyzed tiny differences in the sequences of the genes and determined that differences in just one of the GABA-receptor genes, GABRA2, were associated with alcoholism. The same gene was associated with the brainwave patterns.

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Edenberg is director of the Center for Medical Genomics at IU, where the genotyping for this study was performed. The Center's resources were funded in large part by the Indiana Genomics Initiative, as well as the state of Indiana's 21st Century Research and Technology Fund.