Why some people like booze more than others

Scientists have identified a previously unknown genetic mechanism connecting the brain and the liver that might help explain why some people like alcoholic drinks more than others.

The new research by an international team of scientists has shown through a combination of studies involving humans and mice that variations in the gene called beta-klotho (KLB), regulates alcohol-drinking behaviour.

The scientists conducted what is known as a genome-wide association study among 105,000 people of European ancestry and found that a specific variant of KLB is associated with increased alcohol consumption - people with this variant tend to drink more than those without this variant. They also observed that mice with their KLB genes knocked out guzzled far larger amounts of alcohol than mice with intact KLBs.

Their findings, published today in the US research journal Proceedings of the National Academy of Sciences, raise what the scientists say is an "intriguing possibility" of a biological pathway linking the liver to the brain and influencing behaviour.

"This is something not seen before - a gene made in the liver travels to the brain and influences alcohol drinking behaviour," Gunter Schumann, chair of biological psychiatry at King's College, London, who led the research, told The Telegraph on phone.

Scientists have known for decades that alcohol drinking is a heritable complex trait, likely influenced by multiple genes. But how specific genes influence brain functions that affect drinking has been hard to pinpoint because, as with other complex traits, the effect of each individual gene is small and hard to recognise with small samples.

Most of the earlier studies examined specific genes linked to alcohol-dependence based on existing knowledge of how alcohol is broken down in the body. Schumann and his colleagues used one of the largest human population samples for alcohol-genetics research to look for all new genes, without pre-existing hypothesis.

While the precise mechanism of how KLB influences behaviour is not known, Schumann said it is possible that it involves the brain's reward circuitry that is activated through various stimuli including alcohol.

"Our results suggest that when we knock out the KLB gene in the mice, the animals experience alcohol drinking as more rewarding," he said.

The connection between KLB gene and severe forms of alcohol drinking are still to be explored. But the new findings raise the possibility that that the biological pathway involving the KLB protein and its liver-brain link may be a potential pharmaceutical target, guiding the search for drugs to curb cravings for alcohol.

"This is a possibility," Schumann said. "While there currently exist several anti-craving medications, they have a different mechanism of action. Targeting the pathway identified by our study might provide an alternative way to tackle alcohol-use disorders."

More than 120 researchers from academic institutions in Austria, Finland, Germany, Italy, the UK and the US, among other countries, collaborated in the mammoth study. The laboratory studies on mice were conducted at the University of Texas Southwestern Medical Centre, Dallas.

Scientists say the use of a genome-wide association study - in which whole genomes are compared for specific traits or diseases - and the large sample size, both, make it significant.

"A genome-wide association study is a useful strategy to look for new genes and the underlying biological pathways associated with a disease or a trait," said Kumarasamy Thangaraj, a senior population geneticist at the Centre for Cellular and Molecular Biology, Hyderabad, who was not associated with the study.

"Their sample of more than one lakh individuals is huge - the larger the sample, the greater is the confidence in the results," said Thangaraj, who had earlier identified genetic variations in sections of Indian populations that appear to slow down alcohol breakdown in the body.

People who possess these variations are likely to experience the intoxicating effects of alcohol longer than people without these variations, he said.

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