Scientists have identified new genetic variants that affect the progression of Crohn's disease, a chronic inflammatory bowel disease for which there is currently no cure. Surprisingly, these variants differed from the ones that increase risk of an individual developing the disease in the first place.
In the UK, roughly 115,000 people suffer from Crohn's disease. This is a long-term condition which causes an inflammation of the lining of the digestive system - usually a section of the small intestine or the large intestine. Symptoms include abdominal pain, diarrhoea, fever and weight loss.
Like all chronic disease it is characterised by periods of acute symptoms followed by periods of remission and can gradually worsen over time.
This means that for most patients, their wellbeing is not directly linked to the diagnosis itself, but to the course that the disease takes over time - the "prognosis".
There are significant prognosis variations between people that remain poorly documented, even though genetic causes for the disease have previously been identified.
Thus, finding out what causes the disease to progress differently from one patient to the next was the aim of the study published in Nature Genetics. The scientists, from the University of Cambridge, thought that genetics might be involved.
"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 lead author 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."
Diagnosis vs prognosis
The team conducted a genome-wide association study in two cohorts of patients with Crohn's disease. More than 2,700 patients with very different forms of the disease were included in the analysis.
The researchers compared the DNA of patients who had particularly mild or particularly aggressive Crohn's disease. The analysis revealed four different genetic variants that appeared to influence the severity of a patient's condition and how fast the disease progressed.
The scientists then compared these variants to the 170 disease susceptibility loci - the regions on chromosomes highly susceptible to mutations linked with the development of Crohn's disease. They discovered that none of the four variants had previously been shown to affect the risk of developing the condition.
This suggests that variants for Crohn's disease diagnosis and prognosis are independent from one another. However, some of these variants had been associated with other autoimmune diseases, including rheumatoid arthritis. This knowledge could provide researchers with fresh clues to find therapeutic options for patients.
"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," concludes Lee. "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."