Different genes affect severity or risk of Crohn's
January 2017: Researchers identify genetic variants that affect the severity of Crohn's disease - but none indicate level of risk of developing the condition.
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.
Crohn's disease is one of a number of chronic 'complex' diseases for which there is no single gene that causes the disease. To date around 170 genetic variants have been identified that increase the risk of an individual developing the disease. The conventional wisdom has been that there is a threshold: 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 be.
However, in a study published in Nature Genetics, a team of researchers including CGEM’s Professor Jack Satsangi, has shown that this is not the case: genetic variants that affect the progression of a disease operate independently of those that increase the likelihood of developing the disease in the first place.
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 the DNA of patients in both groups, 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 in the first place.
The team then looked at all the known genetic variants which indicate the risk of developing Crohn's, and found that none of these influenced the severity of disease.
This demonstrates that the biological pathways driving disease progression may be very different to those that initiate the disease itself, with one set of genetic variants influencing the onset of the disease, and an entirely different set affecting disease severity.
This discovery has shown us a new way of looking at disease and opens up potential new treatment options, which could substantially ease the burden of Crohn's disease. What's more, we have evidence that some of these prognosis genes will be shared with other diseases, and as such this approach could be used to improve treatment in a number of conditions.
Journal article: Lee et al., Nature Genetics 49, 262–268 (doi:10.1038/ng.3755)