Researchers at Karolinska Institutet have identified additional genetic factors underlying fat accumulation in the liver. In a study published in the journal Nature Genetics, 60 genetic regions linked to the amount of fat in the liver were identified, 31 of which had not previously been associated with fatty liver disease.
Fatty liver disease is characterized by the accumulation of triglycerides – a type of fat – in the liver. The disease has a strong genetic component, but until now, knowledge about which genes influence its development has been limited. To gain a better understanding, the researchers analyzed genetic data and MRI scans from 71,488 people of European descent in the British UK Biobank database. This is the largest study to date in which researchers have examined the entire genome while simultaneously measuring liver fat levels using MRI.
New genes identified as potential key players
The researchers identified 60 independent genetic regions linked to liver fat levels. Of these, 31 had not previously been reported for this trait. The study estimates that common genetic variants can explain about 25 percent of the differences in liver fat between individuals.
Photo: Rickard Kilström
“By nearly doubling the number of known genetic regions linked to liver fat, we gain a more detailed understanding of the biological mechanisms underlying fatty liver disease,” says Stefano Romeo , professor at the Department of Medicine, Huddinge , Karolinska Institutet.
The researchers also used various methods to identify which genes are likely affected by the genetic variations. For 48 of the 60 genetic regions, they were able to identify genes that likely play a role in the development of fatty liver disease.
The researchers also developed a genetic risk scale based on numerous genetic variants. Individuals with the highest genetic risk were more likely to develop fatty liver disease and liver cancer compared to those with the lowest genetic risk. The results suggest that hereditary factors affecting fat accumulation in the liver may also play a role in the development of liver disease later in life.
The researchers emphasize that the study included only individuals of European descent. To determine whether the results apply to other population groups as well, larger studies across multiple populations are needed. In addition, several of the newly identified genetic regions need to be confirmed in future studies.
See the study for funding information and any conflicts of interest.
Publication
“Genome-wide association study identifies 60 loci associated with liver triglyceride content”, Oveis Jamialahmadi, Shahir Mowlaei, Kyla Gelev, Rosellina M. Mancina, Valentina Flagiello, Julia Kozlitina, Päivi Pajukanta, Luca Valenti, and Stefano Romeo, Nature Genetics, online October 21, 2026, doi: 10.1038/s41588-026-02794-6
