40% of risk of fatal bowel disease is inherited

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Researchers at the University of Queensland have used genetics to show that much of the risk of developing a common and sometimes fatal bowel disease is inherited.

Dr. Yeda Wu and Professor Naomi Ray From UQ Institute of Molecular Life Science Intestinal diverticular disease (DivD) has been studied as an overlooked and understudied cause of the disease, which is prevalent in Australia, particularly among older people.

A genome-wide association study of more than 700,000 people showed that DivD is highly heritable, with 150 genetic factors associated with the risk of developing the disease.

Dr. Wu said that until now, a low-fiber diet was thought to be the main risk factor for DivD.

“We were very surprised to learn that 40% of the risk for intestinal diverticular disease is inherited,” Dr. Wu said.

Diverticula are bag-like growths in the wall of the intestinal tract that affect 33% of people aged 50 to 59, rising to 71% of people aged 80 and older.

“A quarter of people with diverticula develop symptoms and complications, such as abscesses and bleeding, which can be life-threatening,” Dr. Wu said.

“Our results should allow us to use genetics as a tool to identify people at high risk of developing DivD.

“They could then be monitored more closely by their GP and advised on dietary and lifestyle changes to lower their risk.”

Professor Ray said the study revealed that genes related to the structure of the colon, the intestinal mucus layer and the process of moving food through the intestine are involved in DivD.

“We also found that these genes were highly correlated with genes for other gastrointestinal diseases, such as irritable bowel syndrome,” Professor Ray said.

“One gene encodes a drug target for the treatment of IBS constipation, and this is sufficient justification for this type of research to find existing treatments that may also be effective for this disease. It’s about how you can use it.”

“This method can also be used to identify other drug targets, opening the door to more effective treatment strategies than antibiotics or surgical removal of the colon.”

The study also showed that people with DivD ate less whole grains and bread, ate less fruits and vegetables, and drank less water than people without DivD.

“While genetic discoveries have implications for future DivD treatment and prevention, there is still a clear link between food intake and DivD,” Dr. Wu said.

“This is consistent with healthy eating recommendations for optimal bowel function and health.”

reference: Wu Y, Goreva SB, Breidenbach LB, et al. 150 risk variants for intestinal diverticular disease prioritize cell types and enable polygenic prediction of disease susceptibility. cell genomics. 2023:100326. Doi: 10.1016/j.xgen.2023.100326

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