A gene mutation for excessive alcohol drinking found

November 26, 2013

UK researchers have discovered a gene that regulates alcohol consumption and when faulty can cause excessive drinking. They have also identified the mechanism underlying this phenomenon.

The study showed that normal show no interest in and drink little or no alcohol when offered a free choice between a bottle of water and a bottle of diluted alcohol.

However, mice with a genetic mutation to the gene Gabrb1 overwhelmingly preferred over water, choosing to consume almost 85% of their daily fluid as drinks containing alcohol.

The consortium of researchers from five UK universities – Imperial College London, Newcastle University, Sussex University, University College London and University of Dundee – and the MRC Mammalian Genetics Unit (MGU) at Harwell, funded by the Medical Research Council (MRC), Wellcome Trust and ERAB, publish their findings today in Nature Communications.

Dr Quentin Anstee, Consultant Hepatologist at Newcastle University, joint lead author said: "It's amazing to think that a small change in the code for just one gene can have such profound effects on complex behaviours like alcohol consumption.

"We are continuing our work to establish whether the gene has a similar influence in humans, though we know that in people alcoholism is much more complicated as environmental factors come into play. But there is the real potential for this to guide development of better treatments for alcoholism in the future."

Working at the MRC Mammalian Genetics Unit, a team led by Professor Howard Thomas from Imperial College London introduced subtle mutations into the genetic code at random throughout the genome and tested mice for alcohol preference. This led the researchers to identify the gene Gabrb1 which changes alcohol preference so strongly that mice carrying either of two single base-pair point mutations in this gene preferred drinking alcohol (10% ethanol v/v - about the strength of wine), over water.

The group showed that mice carrying this mutation were willing to work to obtain the alcohol-containing drink by pushing a lever and, unlike normal mice, continued to do so even over long periods. They would voluntarily consume sufficient alcohol in an hour to become intoxicated and even have difficulty in coordinating their movements.

The cause of the was tracked down to single base-pair point mutations in the gene Gabrb1, which codes for the beta 1 subunit, an important component of the GABAA receptor in the brain. This receptor responds to the brain's most important inhibitory chemical messenger (GABA) to regulate brain activity.

The researchers found that the gene mutation caused the receptor to activate spontaneously even when the usual GABA trigger was not present.

These changes were particularly strong in the region of the brain that controls pleasurable emotions and reward, the nucleus accumbens, as Dr Anstee explains: "The mutation of the beta1 containing receptor is altering its structure and creating spontaneous electrical activity in the brain in this pleasure zone, the nucleus accumbens. As the electrical signal from these receptors increases, so does the desire to drink to such an extent that mice will actually work to get the alcohol, for much longer than we would have expected."

Professor Howard Thomas said: "We know from previous human studies that the GABA system is involved in controlling alcohol intake. Our studies in mice show that a particular subunit of GABAA receptor has a significant effect and most importantly the existence of these mice has allowed our collaborative group to investigate the mechanism involved. This is important when we come to try to modify this process first in mice and then in man."

Initially funded by the MRC, the 10-year project to find genes affecting was led by Professor Howard Thomas from Imperial College London and initiated at the MRC Mammalian Genetics Unit. The consortium now involves researchers at five UK universities - Imperial College London, Newcastle University, Sussex University, University College London and the University of Dundee. Senior investigators are Dr Quentin Anstee at Newcastle University and Dr Susanne Knapp at Imperial College London (joint lead authors); Professor Dai Stephens at Sussex University; Professor Trevor Smart at University College London; Professor Jeremy Lambert and Dr Delia Belelli at the University of Dundee; and Professor Steve Brown at the MRC Mammalian Genetics Unit.

Professor Hugh Perry, Chair of the MRC's Neurosciences and Mental Health Board, said: "Alcohol addiction places a huge burden on the individual, their family and wider society. There's still a great deal we don't understand about how and why consumption progresses into addiction, but the results of this long-running project suggest that, in some individuals, there may be a genetic component. If further research confirms that a similar mechanism is present in humans, it could help us to identify those most at risk of developing an addiction and ensure they receive the most effective treatment."

Explore further: Study identifies gene for alcohol preference in rats

More information: Anstee, Q. M. et al. Mutations in the Gabrb1 gene promote alcohol consumption through increased tonic inhibition. Nat. Commun. 4:2816 DOI: 10.1038/ncomms3816 (2013).

Related Stories

Study identifies gene for alcohol preference in rats

October 1, 2013
(Medical Xpress)—Selectively bred strains of laboratory rats that either prefer or avoid alcohol have been a mainstay of alcohol research for decades. So-called alcohol-preferring rats voluntarily consume much greater amounts ...

Teens who drink alone more likely to develop alcohol problems as young adults

November 18, 2013
Most teenagers who drink alcohol do so with their friends in social settings, but a new study by researchers at Carnegie Mellon University and the University of Pittsburgh reveals that a significant number of adolescents ...

Tendency to binge drinking runs in the blood

November 8, 2012
Mice drink more alcohol during the dark cycle compared to daytime.  The discovery made by scientists from  Portland Alcohol Research Center and The Beckman Institute for Advanced Science and Technology at University of ...

Scientists identify promising target for development of new alcohol abuse medications

November 27, 2012
(Medical Xpress)—Decreasing the level of a key brain protein led to significantly less drinking and alcohol-seeking behavior in rats and mice that had been trained to drink, according to a study by researchers at the Ernest ...

New strain of lab mice mimics human alcohol consumption patterns

December 12, 2011
A line of laboratory mice developed by a researcher from the School of Science at Indiana University-Purdue University Indianapolis drinks more alcohol than other animal models and consumes it in a fashion similar to humans: ...

Recommended for you

Genetic variants found to play key role in human immune system

August 16, 2017
It is widely recognized that people respond differently to infections. This can partially be explained by genetics, shows a new study published today in Nature Communications by an international collaboration of researchers ...

Active non-coding DNA might help pinpoint genetic risk for psychiatric disorders

August 16, 2017
Northwestern Medicine scientists have demonstrated a new method of analyzing non-coding regions of DNA in neurons, which may help to pinpoint which genetic variants are most important to the development of schizophrenia and ...

Evolved masculine and feminine behaviors can be inherited from social environment

August 15, 2017
The different ways men and women behave, passed down from generation to generation, can be inherited from our social environment - not just from genes, experts have suggested.

Attitudes on human genome editing vary, but all agree conversation is necessary

August 10, 2017
In early August 2017, an international team of scientists announced they had successfully edited the DNA of human embryos. As people process the political, moral and regulatory issues of the technology—which nudges us closer ...

Two genes help older brain gain new cells

August 10, 2017
Two genes act as molecular midwives to the birth of neurons in adult mammals and when inactivated in mice cause symptoms of Fragile X Syndrome, a major cause of mental retardation, a new Yale University study has shown.

New technique searches 'dark genome' for disease mutations

August 10, 2017
When doctors can't find a diagnosis for patient's disease, they turn to genetic detectives. Equipped with genomic sequencing technologies available for less than 10 years, these sleuths now routinely search through a patient's ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

QuixoteJ
5 / 5 (1) Nov 26, 2013
Or, they just discovered the gene mutation that causes coolness.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.