A new study from researchers at Mayo Clinic has revealed an important discovery about a common liver disease that affects millions of people around the world.
Scientists have identified a rare inherited genetic mutation that may directly cause metabolic dysfunction-associated steatotic liver disease, or MASLD, which was previously known as nonalcoholic fatty liver disease.
The findings offer a new way of understanding how this disease develops and could eventually lead to more personalized treatments for patients.
The research was published in the medical journal Hepatology. The study was led by researchers at Mayo Clinic’s Center for Individualized Medicine, together with scientists from the Medical College of Wisconsin.
MASLD is one of the most common liver diseases in the world today. It affects around one in three adults globally. The disease happens when too much fat builds up inside the liver. In many cases, people may not notice symptoms at first. However, over time, the condition can become dangerous.
Fat buildup in the liver can trigger inflammation and damage liver tissue. This can eventually lead to scarring, known as fibrosis, and in more severe cases, cirrhosis. Cirrhosis is a serious condition where the liver becomes badly scarred and loses its ability to work properly. This can increase the risk of liver failure and liver cancer.
Doctors have long believed that MASLD develops because of a combination of factors such as obesity, poor diet, diabetes, lack of exercise, and genetics.
Usually, scientists thought many genes and lifestyle factors worked together to increase risk. But this new study shows that in some people, a single inherited mutation may play a major role in causing the disease.
The discovery centers on a gene called MET. This gene is important because it helps control liver repair and fat processing inside the body.
Researchers found that when this gene is damaged by a rare mutation, the liver struggles to process fat correctly. As a result, fat starts building up in liver cells, leading to inflammation and progressive liver damage.
The study began when doctors examined a woman and her father who both had a severe form of MASLD called metabolic dysfunction-associated steatohepatitis, or MASH.
MASH is a more advanced and dangerous stage of fatty liver disease because it involves both fat buildup and ongoing inflammation. Surprisingly, the two patients did not have many of the usual risk factors linked to the disease. They did not have conditions like diabetes or high cholesterol that are commonly associated with liver fat problems.
Because the cases were unusual, the research team decided to investigate their DNA more closely. Scientists studied more than 20,000 genes in the patients and eventually found a tiny mutation in the MET gene. The mutation involved a change in just one “letter” of the genetic code, but it had a major effect on how the liver handled fat.
To confirm the discovery, Mayo Clinic researchers partnered with experts at the Medical College of Wisconsin. Dr. Raul Urrutia and his team showed that the mutation disrupted the normal instructions carried by the gene.
This caused problems in fat metabolism and interfered with normal liver function. What made the finding even more remarkable was that this mutation had never been recorded before in major scientific genetic databases.
Dr. Filippo Pinto e Vairo, the lead author of the study and medical director of Mayo Clinic’s Program for Rare and Undiagnosed Diseases, said the discovery provides an entirely new understanding of how rare inherited genetic changes can contribute to diseases that are usually considered common conditions.
He explained that this research opens the door to future treatment possibilities and more targeted medical care.
The researchers then wanted to know whether rare MET mutations might also be affecting other people with liver disease. To explore this question, they used data from Mayo Clinic’s Tapestry study, a large genetic research project involving more than 100,000 people across the United States.
Among nearly 4,000 adults in the Tapestry study who had MASLD, researchers discovered that around 1% carried rare variants of the MET gene.
Even more importantly, nearly one in five of those individuals had mutations located in the exact same area of the gene as the original family in the study. This strongly supports the idea that problems in the MET gene may directly contribute to fatty liver disease in some patients.
Dr. Konstantinos Lazaridis, director of Mayo Clinic’s Center for Individualized Medicine and one of the lead researchers, said the discovery may have major global importance because millions of people worldwide suffer from MASLD.
He explained that large-scale genetic databases like the Tapestry study are becoming powerful tools for uncovering hidden causes of common diseases.
The findings also highlight the growing importance of personalized medicine. Instead of treating every patient in the same way, personalized medicine aims to understand the unique genetic and biological factors behind each person’s illness.
This approach may help doctors identify high-risk patients earlier and choose treatments that work best for them.
Mayo Clinic has been expanding its work in this area for years. Since 2019, its Program for Rare and Undiagnosed Diseases has helped more than 3,200 patients with difficult-to-diagnose conditions.
The program works with hundreds of medical specialists to use advanced genetic tools to solve medical mysteries that traditional testing often cannot explain.
Researchers believe the next step will be learning more about how MET mutations damage the liver and whether new treatments can target these specific genetic problems.
In the future, doctors may be able to identify people carrying these mutations before severe liver damage develops. Earlier diagnosis could help prevent cirrhosis, liver failure, or liver cancer.
This study not only changes how scientists think about MASLD but also shows how hidden genetic causes may exist behind many other common diseases. It demonstrates how modern genetic research is helping doctors move closer to more precise and individualized healthcare.
If you care about liver health, please read studies about simple habit that could give you a healthy liver, and common diabetes drug that may reverse liver inflammation.
For more information about health, please see recent studies about simple blood test that could detect your risk of fatty liver disease, and results showing this green diet may strongly lower non-alcoholic fatty liver disease.
Copyright © 2026 Knowridge Science Report. All rights reserved.
