Recent research points toward a specific gene that’s responsible for binge drinking behavior. 

UT Southwestern researchers David Mangelsdorf and Steven Kliewer have been studying a protein called β-Klotho for over ten years, which plays a role in moderating a person’s desire for alcohol. They recently teamed up with 108 research institutions on an alcohol preference study of over 100,000 people in Europe. 

Mangelsdorf and Kliewer’s lab studies mice to see exactly how the β-Klotho protein functions in living organisms. 

The protein is part of a signaling pathway in both humans and mice that affects an individual’s inclination for alcohol. 

“If you eliminate this gene, animals drink more alcohol than they normally would if they’re given the choice between alcohol-laced water and regular water,” Mangelsdorf said. 

For the large-scale study, researchers surveyed both frequent and non-frequent drinkers, through a genome-wide association analysis, which involves sampling the participants’ DNA and looking for variations in their genes that could account for drinking behavior. 

“(The other researchers) took samples of DNA and looked for variations in their genetic makeup that might be associated with binge drinking behaviors, and they found something in the genes that our lab studies,” Mangelsdorf said. “That was the gene that encodes for β-Klotho.”  

The results of these tests pointed towards the β-Klotho protein as the main force controlling people’s craving for alcohol. 

“β-Klotho, when activated in the brain, suppresses your desire to drink alcohol,” Mangelsdorf said. 

Kliewer said the protein acts as a coreceptor for the hormone FGF21, which is excreted by the liver. 

Mangelsdorf said roughly 60 percent of participant genomes had the variation that makes alcohol more desirable, while the remainder had the variation that decreases their alcohol cravings. 

Historically, food fermentation was a simple way to prevent foods from decaying and collecting bacteria, so most food tested from before refrigeration contains traces of alcohol, Mangelsdorf said. He added that alcohol was often used medicinally, in order to decrease the chance of infection. 

“No one had anticipated that the β-Klotho pathway would affect alcohol consumption. And since this pathway can be activated by FGF21, this may be an entirely new way to treat alcohol addiction,” Kliewer said.  

The β-Klotho receptor still has more outlets to be explored in the future to take an even deeper look into this behavior changing gene. 

“We’re now focused on understanding precisely how FGF21 acts on the brain to suppress the desire to drink alcohol,” Kliewer said.