81 genetic variants advance researchers’ knowledge about hernia

Diet and lifestyle 30. aug 2022 3 min Senior Researcher Frank Geller Written by Kristian Sjøgren

Analysis of the genetics behind hernia indicates that variation in the genes associated with connective tissue structure strongly influences the risk of developing hernia. The discovery provides greater insight into hernia as a disease and how to identify people with the greatest risk of developing it.

More than 10,000 hernia operations are performed each year in Denmark. Worldwide, the figure is several million.

Researchers have hypothesised that the development of hernia has a genetic component that makes some people more predisposed than others. Researchers have now obtained a better understanding of this genetic component.

In a new study published in Nature Communications, researchers have identified 81 genetic variants that increase the risk of developing hernia.

The 81 genetic variants could be utilised to identify individuals at high risk of developing a hernia or whether those who have already had a hernia are at risk of developing it again.

“Our study can form the basis for clinical studies that link the genetics behind hernia to the pathology. This will enable us to better understand why some people develop hernias, where they develop hernias and to what extent they develop hernias,” explains a researcher behind the study, Frank Geller, Senior Researcher, Department of Epidemiology Research, Statens Serum Institut, Copenhagen.

Outpouching through the abdominal cavity leads to hernia

A hernia is a protrusion of tissue through the abdominal cavity in places where the abdominal wall in the groin or diaphragm or around the navel is weak. It can manifest as lumps, for example, when you stand up or cough.

A hernia can also contain part of the intestine, which is at risk of being trapped in the pouch. In this case, immediate surgical intervention is necessary, and in general, most types of hernia are treated by surgery.

The five most common types of hernia are inguinal, diaphragmatic, umbilical, femoral and ventral.

In the new study, Frank Geller and colleagues obtained data on 500,000 people in the UK Biobank to determine whether genetic variants are associated with increased risk of developing the five types of hernia.

Genetic variants are tiny changes in the genome that can cause genes to behave slightly differently than they should.

“Previous studies have identified four genetic variants that are associated with an increased risk of developing an inguinal hernia, but we expected to be able to find more if we looked at larger data sets,” says Frank Geller.

Examined data from more 500,000 people

In the UK Biobank, the researchers found data on 65,492 people who had had a hernia. The vast majority had either an inguinal hernia (more than 30,000 people) or a diaphragmatic hernia (also more than 30,000 people), the two most common types of hernia.

The researchers looked for genetic differences between people with and without hernia and between the different types of hernia.

The aim was to identify genetic variants that predispose to hernia in general and to the different types of hernia individually.

The researchers subsequently confirmed their findings in population data from Denmark, Finland and Estonia.

81 genetic variants that increase the risk of hernia

The results show that 81 genetic variants are associated with an increased risk of developing a hernia, but each of these variants only has a small to moderate effect.

Further review of the data also showed that 26 genetic variants are associated with an increased risk of developing several different types of hernia. According to Frank Geller, this indicates a substantial genetic overlap between the underlying mechanisms.

The researchers also studied the function of the genes in which the genetic variants for hernia are located and found that several of the genetic variants are located in genes associated with connective tissue structure.

This applies to genes for elastin and collagen, which are the proteins from which connective tissue fibres are made. Co-author Bjarke Feenstra, Senior Scientist and Head of Section, Department of Epidemiology Research, Statens Serum Institut, elaborates:

“The genetic variants probably influence the development and maintenance of the structure of the connective tissue and can thereby increase the risk of a rupture, resulting in a hernia. Each genetic variant by itself is not a major risk factor, but if a person’s genome contains many of these variants, in combination they can significantly increase the risk of developing a hernia,” he explains.

Genetic overlap including depression and smoking

The researchers also compared the genetics behind hernia with the genetics behind 245 other diseases and health-relevant traits. They found that the genetics behind hernia overlap with, among other things, higher body-mass index, smoking status and mental disorders such as depression.

“In connection with the large iPSYCH project in Denmark, we examined six psychiatric diagnoses in more detail and found a possible causal link between depression and especially diaphragmatic hernia and, to a lesser extent, ventral hernia,” says Bjarke Feenstra.

According to Frank Geller, the most interesting perspective of the new study is that it opens up for clinical studies that can link the genetics behind hernia to the disease trajectories of individual patients.

One can envision that, based on the discovery of the 81 genetic variants, studies can compare people’s genetic risk of developing a hernia with whether they actually develop it. Thus, an individual risk score can be developed based on something as simple as a blood test and perhaps identify those with the greatest risk of hernia.

“Another interesting possibility could be a follow-up study of patients after surgery for inguinal hernia to investigate whether they later needed surgery again. Such a study may combine genetic information with detailed patient data and information about lifestyle factors and other health conditions or diseases. It will be more complicated than a registry-based research study but may provide exciting, clinically relevant knowledge,” he concludes.

Frank Geller is a senior researcher in the Genetic Epidemiology Group at Statens Serum Institut (SSI). His research is focused on the identification o...

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