A hormone link between the brain and the liver may control people’s alcohol consumption – depending on which version they carry of a particular gene. This could be a target for treatments that reduce the desire for alcohol in problem drinkers.
So concludes a large international team – including members from King’s College London in the United Kingdom – after it carried out the biggest ever genetic analysis of non-addictive alcohol consumption, a report of which can be found in the Proceeding of the National Academy of Sciences.
Paul Elliott, one of the senior investigators and a professor in the School of Public Health at Imperial College London in the U.K., says:
“Alcohol drinking in excess is a major public health problem worldwide and we need to find new ways of reducing the harmful effects of alcohol in the population. Even small shifts downward in the average amount of alcohol people drink may have major health benefits.”
According to the World Health Organization (WHO), in 2012, about 3.3 million deaths – or 5.9 percent of all deaths worldwide – were attributable to alcohol consumption.
Alcohol consumption is a causal factor in over 200 disease and injury conditions. A significant proportion of this burden arises from unintentional and intentional injuries, such as from road traffic collisions, violence, and attempted suicides – with fatal alcohol-related injuries being more common among younger people.
Although drinking habits are known to be inherited, not many genes that are clearly linked to alcohol drinking have been identified.
One problem that makes it difficult to identify single genes that affect how the brain influences alcohol consumption is that their effect is so small that you have to do very large studies to find them.
For the new research, the team pooled and analyzed data from genome-wide studies on over 105,000 individuals of European descent who had also filled in surveys about their drinking habits.
The results showed that variations in a gene called β-Klotho were linked to the amount of alcohol the study participants consumed – suggesting the gene could be an influence on drinking behavior.
The researchers observed that the less common β-Klotho gene variant – present in about 40 percent of the participants – was tied to a lower desire to drink alcohol.
Further investigation revealed that mice without the β-Klotho gene in their brains showed significantly higher preference for alcohol than mice with the gene, suggesting β-Klotho may help control alcohol consumption.
The researchers then looked at what happens to a liver hormone called FGF21 that under normal conditions inhibits alcohol preference in mice.
They found FGF21 had no effect on drinking behavior in mice without β-Klotho, suggesting FGF21’s influence depended on the gene.
They also found that, unlike mice with β-Klotho, those without the gene showed no differences in measures of anxiety, a possible route through which drinking behavior might be affected.
The researchers say the findings suggest there could be a feedback loop where the liver produces FGF21 in response to sugar and alcohol intake, and this acts on the brain to limit consumption.
However, only further genetic studies will be able to find out whether β-Klotho regulates the pathway directly, or via effects on neighboring genes.
Also, only further studies can show whether this same pathway is involved in more severe forms of alcohol consumption, as the team only investigated non-addictive alcohol consumption.
“The results of our study point to a previously unrecognized genetic determinant of alcohol drinking among the general population. Our findings may eventually lead to new treatments for people whose health is being harmed by drinking.”
Prof. Paul Elliott