Alcohol-Dependence Gene Identified

GABRG3 Has a Consistent Association With Alcohol Dependence

DNA Chart
Alcoholism Gene Identified. © Getty Images

Scientists analyzing DNA from more than 10,000 individuals participating in alcohol treatment programs and their families have identified a gene that appears to be linked to an increased risk of alcoholism.

The gene is related to a receptor that allows for the movement of Gamma-amino butyric acid (GABA) between nerve cells. GABA is the major inhibitory chemical in the central nervous system.

The study is the first to find a link between this particular gene and alcohol dependence, the researchers said.

Genes and the Effects of Alcohol

"There were lines of evidence from other studies -- animal studies, in vitro studies -- that suggested GABA receptors are involved in the behavioral effects of alcohol," says lead author Danielle M. Dick, Ph.D., research assistant professor of psychiatry at Washington University School of Medicine in St. Louis. "Because GABA receptor genes were likely candidates and previous studies had linked this area on chromosome 15 to alcoholism, we zeroed in on three GABA receptor genes but only found significant association with one of them."

The national Collaborative Study on the Genetics of Alcoholism (COGA) is an project involving interviews and DNA samples from more than 10,000 individuals from inpatient and outpatient alcohol treatment centers and their families. Families in the COGA study usually have several members with alcohol dependence.

Alcohol Gene Identified

This study is part of the COGA project.

The researchers analyzed DNA from 262 families, a total of 2,282 individuals. They isolated three genes on chromosome 15 -- GABRA5, GABRB3 and GABRG3 -- that sit very close together on the chromosome.

Using markers called SNPs (single nucleotide polymorphisms), they examined the differences between the participants' genes.

How It Influences Risk Is Not Known

The markers demonstrated small genetic differences did appear to influence the risk of alcohol dependence, but only in one of the genes: GABRG3.

"It is not known how GABRG3 influences alcoholism risk," the researchers said. "Previous research has suggested chemicals that increase GABA receptor activity can accentuate the behavioral effects of alcohol, such as sedation, loss of anxiety and problems with motor coordination. Conversely, chemicals that decrease GABA receptor activity can have the opposite effect.

Pathway to Alcoholism?

"This suggests that somehow GABA reception might be involved in these behavioral effects," Dick says. "But we don't know exactly how, so we can't tell what the pathway might be that leads from GABA receptor genes to alcoholism."

"Finding that GABA is involved in alcohol abuse and dependence supports a current theory that predisposition to alcoholism might be inherited as part of a general state of brain overactivation," Dick said.

"People at risk for alcoholism may inherit a variety of genes that contribute to this state. Perhaps alcohol normalizes that state of excitability, leading people with a hyperexcited nervous system to use alcohol more frequently in order to normalize brain circuits. That, in turn, would put them at greater risk for developing alcohol dependence."

Not Doomed to Become Alcoholic

He said it is important to point out that genetic make-up does not necessarily mean a person is doomed to become an alcoholic.

"One reason it is so difficult to find genes involved in psychiatric disorders is that there is an interplay between genetic and environmental factors," she says. "A person can carry all kinds of genes that predispose them to alcohol dependence, but if they never take a drink, they won't become an alcoholic."


Dick, DM, et al. "Association of GABRG3 With Alcohol Dependence." Alcoholism: Clinical & Experimental Research January 2004

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