31 New Genetic Regions Linked to Fatty Liver Disease, Study Finds
Researchers at Karolinska Institutet in Sweden have identified 31 previously unknown genetic regions linked to liver fat levels, nearly doubling the number of known genetic factors behind fatty liver disease.
The study, published in Nature Genetics, analysed genetic data and MRI scans from 71,488 people of European descent in the UK Biobank. It is the largest study to examine the entire genome alongside MRI-based measurements of liver fat.
What the study found
Fatty liver disease occurs when triglycerides, a type of fat, accumulate in the liver. Genetics play an important role in the condition, but scientists have not fully understood which genes drive its development.
The research team identified 60 genetic regions associated with liver fat levels. Of these, 31 had not previously been linked to this trait. The study estimates that common genetic differences account for around 25 per cent of the variation in liver fat levels between individuals.
The researchers also worked out which genes were likely affected by these variations, identifying probable disease-related genes in 48 of the 60 regions.
“By almost doubling the number of known genetic regions linked to liver fat, we get a clearer picture of the biological processes behind fatty liver disease,” said Stefano Romeo, a professor at Karolinska Institutet’s Department of Medicine in Huddinge.
The team also built a genetic risk score from many individual variants. People with the highest scores were more likely to develop fatty liver disease and liver cancer than those with the lowest scores.
According to the Nature Genetics paper, 14 of the 31 newly identified signals were confirmed in a separate analysis of clinically diagnosed metabolic dysfunction-associated steatotic liver disease, covering 42,163 cases and more than 1.6 million controls. The researchers also found that the increase in risk was nearly three times greater for liver cancer than for cirrhosis among those with the highest inherited risk.
How the study was done
The researchers combined genetic data with MRI scans that measured liver fat directly. Rather than relying on blood tests or diagnosis records alone, they used MRI-derived proton density fat fraction readings to quantify the amount of fat in each participant’s liver.
The analysis pooled three UK Biobank imaging datasets, adjusting for age, sex, body mass index and other factors, so the results reflect genetic effects beyond general body weight.
An important limitation
The researchers are clear about one weakness: the study included only people of European descent. Whether the findings apply to other populations is still unknown.
That matters for readers in Pakistan. Genetic risk factors can differ substantially between ancestries, which is why the researchers say larger studies across multiple populations are needed.
For now, the study is a map of the biology behind fatty liver disease, not a personal risk calculator for any individual.
What comes next
The newly identified regions give drug researchers fresh targets. If some of the 48 candidate genes turn out to drive fat accumulation in the liver, they could become the basis for therapies that slow or reverse the disease before it progresses to cirrhosis or cancer.
The genetic risk score could one day help identify high-risk people for closer monitoring, but clinical use remains a long way off.
For more on liver and metabolic health, read our coverage of the three hidden risks behind deadly liver disease, weight-loss injections and what to know about them, why 60 per cent of Pakistanis cannot afford a healthy diet, and the Rs45 billion in health projects approved for Punjab.
Sources: Nature Genetics, News-Medical
Frequently asked questions
What is fatty liver disease?
Fatty liver disease occurs when triglycerides, a type of fat, build up in the liver. Over time it can progress to inflammation, scarring of the liver (cirrhosis) and liver cancer.
What did the Karolinska study discover?
It identified 60 genetic regions linked to liver fat levels, 31 of them new, and found that common genetic variants explain about 25 per cent of the variation in liver fat between people.
Does this apply to people in Pakistan?
Not necessarily. The study included only people of European descent, and the researchers say larger studies in more diverse populations are needed before the results can be generalised.
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Image note: real photo — a clinician reviewing an abdominal MRI scan or a medical illustration of the liver (licensed stock or institutional image). No AI-generated imagery.
