Crohn’s disease risk and prognosis determined by different genes, study finds

11/01/2017

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Researchers have identified a series of genetic variants that affect the severity of Crohn’s disease, an inflammatory bowel disease – but surprisingly, none of these variants appear to be related to an individual’s risk of developing the condition in the first place.

 

Genetic studies have been very successful at identifying genetic risk factors for Crohn’s disease, but have told us virtually nothing about why one person will get only mild disease while someone else might need surgery to treat their condition.
  -  James Lee

Crohn’s disease is one of a number of chronic ‘complex’ diseases for which there is no single gene that causes the disease. In fact, to date around 170 common genetic variants have been identified that each increase the risk of an individual developing the disease. The conventional wisdom has been that there exists a ‘tipping point’: if someone has enough of these genes, they become very likely to develop the disease – and the more of the variants they carry, the more the severe the disease will then be.

However, in a study published in Nature Genetics, a team of researchers led by the University of Cambridge has shown that this is not the case: genetic variants that affect the progression, or prognosis, of a disease operate independently of those that increase the likelihood of developing the disease in the first place.

“Genetic studies have been very successful at identifying genetic risk factors for Crohn’s disease, but have told us virtually nothing about why one person will get only mild disease while someone else might need surgery to treat their condition,” says Dr James Lee from the Department of Medicine at Cambridge. “We do know, though, that family members who have the disease often tend to see it progress in a similar way. This suggested to us that genetics was likely to be involved in prognosis.”

The researchers looked at the genomes – the entire genetic makeup – of more than 2,700 individuals, who were selected because they had either had experienced particularly mild or particularly aggressive Crohn’s disease. By comparing these patients’ DNA, the researchers found four genetic variants that influenced the severity of a patient’s condition. Strikingly, none of these genes have been shown to affect the risk of developing the disease.

The team then looked at all the known genetic risk variants for Crohn’s and found that none of these influenced the severity of disease.

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Image:DNA
Credit: Charles Clegg


Reproduced courtesy of the University of Cambridge
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