DNA detectives expose the little devils responsible for diverticular disease

Why do people develop bulges, or pockets, in the large intestine? Using a Danish analytical technique, scientists have obtained new information which may help find an answer.

When people develop a painful, and sometimes extremely dangerous, infection in pockets in the large intestine, there are close links with a distinct genetic ‘cocktail’.

This is shown by new research recently published in the scientific journal Nature Genetics. This study, funded by Lundbeck Foundation, is the result of a collaboration between scientists from Denmark and the USA, and it is based on analyses of DNA from more than 400,000 individuals.

These bulges or pockets in the bowel are called diverticula and they develop in hollow organs – particularly the large intestine. However, they are also seen in other organs such as the oesophagus.

In physiological terms, the internal layer of the organ – which is a mucous membrane – begins to bulge at a weak spot in the surrounding muscle lining.

To a large extent, however, it is a scientific mystery why, in some people and not in others, these diverticula become a breeding ground for infection, which is often extremely painful and can actually be life-threatening if it ends up ‘cutting’ a hole from the intestines into the abdominal cavity.

For the same reason, it can be difficult to treat this inflammatory condition known as diverticulitis.

Delving into databases
This Danish-American study provides new information to aid our understanding of the cause of diverticulitis by identifying 42 gene variants. These gene variants are found in people who have been diagnosed with diverticulitis of the large intestine, but they are only rarely seen in the same combination in other individuals.

And the scientific article in Nature Genetics explains that, in some way or other, these specific 42 gene variants seem to be the troublemakers when it comes to diverticulitis of the large intestine.

“This knowledge puts us in a better position to develop treatments for diverticulitis – and, in the long term, perhaps even work towards potential forms of prevention,” says Associate Professor Tune Pers, the Danish participant in the study. Tune Pers is a Lundbeck Foundation Fellow and is employed at both the NNF Centre for Basic Metabolic Research at the University of Copenhagen and Denmark’s Statens Serum Institut (SSI).

He specialises in statistical analysis of vast volumes of biochemical and DNA data (watch the video at the bottom of this article), and the mathematical detective work which identified the 42 gene variants as the troublemakers responsible for diverticulitis of the large intestine is based on one of his calculation methods.

A clean sheet of paper
Health research is often based on hypotheses – ideas about how to make sense of a problem, and how to tackle it. However, according to Tune Pers, you can also take a different approach and begin with a clean sheet of paper:

“This is what we did here. My American colleagues, from the University of Michigan, used the calculation method I developed to study the genetic profiles of 27,000 people who’ve been diagnosed with diverticulitis of the large intestine. They then compared the data with similar profiles of 380,000 individuals who don’t have the disease,” says Tune Pers.

The researchers gained access to the over 400,000 DNA profiles through the UK Biobank, a major British database. And a similar study performed in the USA was subsequently able to confirm that the 42 gene variants actually play a key role in the development of diverticulitis of the large intestine:

“But we don’t yet know how it’s all connected,” says Tune Pers.

Facts about diverticula
Around 30% of all Danes over the age of 70 have diverticula – bulges or pockets – in the large intestine.
Infection in, or around, these pockets is called diverticulitis.
Fewer than 10 – 15% of individuals with diverticula develop diverticulitis.

For further information:
Henrik Larsen, science journalist at Lundbeck Foundation, +45 2118 6377 or hl@lundbeckfonden.com

 

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