Journal Club

Highlighting recently published papers selected by Academy members

A genetic connection to alcohol consumption

Identifying genes for alcoholism has been tricky due to its complex nature. Now scientists have found a gene in rats linked to increased alcohol consumption and preference that could one day be a potential target for therapies, report findings detailed in the Proceedings of the National Academy of Sciences.

Alcoholism is a moderately to highly heritable disease. Although investigations have discovered several regions in the genome linked with alcoholism, singling out genes linked with complex disorders such as alcoholism is a complicated task. For instance, such disorders may involve many different gene variants that each may contribute only modest effects. Many of these variants may be uncommon or rare, hampering attempts to identify them. Also, which variants a person with such a disorder has may differ greatly across individuals.

To help uncover the genetic roots of alcoholism, neurogeneticist David Goldman at the National Institute on Alcohol Abuse and Alcoholism in Bethesda, Md., and his colleagues experimented with rats bred either to prefer alcohol or to shun it. They sequenced the genomes of both these breeds of rats and discovered variants in four genes were apparently linked with alcohol preference, one of which deactivated the gene Grm2, which encodes metabotropic glutamate receptor 2 (mGluR2) and plays a critical role with regard to the neurotransmitter glutamate.

“Glutamate is intensively studied for its many roles including memory and learning and neuronal damage following brain trauma,” Goldman says.

The researchers discovered rats that genetically lacked mGluR2 showed higher levels of alcohol preference and consumption. They also saw that injecting normal mice with a compound that inhibited mGluR2 led to a significant although possibly short-lived rise in voluntary alcohol drinking.

Goldman noted that glutamate is linked with many functions in the brain. As such, “it is highly likely that this specific genetic source of variation in glutamate neurotransmission will be multiple in its effects,” Goldman says.

A number of drugs already target glutamate neurotransmission. “Understanding that this neurotransmitter is involved in alcoholism and subject to extreme genetic variation could lead to development and therapies,” Goldman says. He cautions however, that their finding “is likely to take years to translate into diagnosis and treatment.”

Categories: Genetics
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