Crohn’s disease gene discovery boosts hope for tailored treatment
SCIENTISTS have discovered variants in genes that increase the risk of developing Crohn’s disease, raising hopes for the development of a cure.
The causes of the condition are little understood but scientists believe it develops from a hyperactive immune response against gut bacteria in people with certain genes.
Drugs are available that improve symptoms, which include diarrhoea, stomach aches, blood in stool, tiredness and weight loss. However, there is no cure and repeated bouts of severe illness are common.
Researchers from the Broad Institute of MIT and Harvard and the Wellcome Sanger Institute, a genomics research centre, studied the genes of 30,000 patients with Crohn’s. These were compared with the genes of 80,000 people without the condition.
The study, published in Nature Genetics, a scientific journal, identified genetic variation within six genes in areas of the genome that had not been previously connected to Crohn’s. Several of these genes are known to play important roles in a type of stem cell in the gut called mesenchymal cells, which make up the bulk of the body’s muscle and ligaments, suggesting that disruption of these cells contributes to intestinal inflammation.
Another variant was found to decrease risk of developing the disease.
Dr Mark Daly, a senior study author from the Broad Institute of MIT and Harvard, said: “In thinking about how to develop new therapies, it’s critical that we can pinpoint the specific genetic variants that increase or decrease a person’s risk. When we discover a disease association to a genetic variant within a gene, we can start running experiments the next day to figure out what the variant, the gene, and the protein it encodes is doing to influence disease risk.
“This puts us on a dramatically faster track for converting those observations into a therapeutic hypothesis.”
Dr Aleksejs Sazonovs, a co-author of the study from the Wellcome Sanger Institute, said: “Most humans will have some of the genetic variants that increase susceptibility to inflammatory bowel disease because they’re so common. These common variants may increase a person’s risk by 10 per cent, for example, but this increased risk doesn’t necessarily lead to disease.
“But some rare variants can make someone four or five times more likely to develop inflammatory bowel disease, so it’s especially important to locate these and understand the biological processes they disrupt.”
Researchers are planning to increase the scale of sampling, in the hope of locating all variants and genes involved in inflammatory bowel disease. It is hoped that the improved data will make finding treatments a more efficient and faster process.
Dr Carl Anderson, a co-author from the Wellcome Sanger Institute, said: “We’ve already begun our next study, which will use exome sequence data from 650,000 individuals and give us unprecedented insights into the aberrant biology underpinning inflammatory bowel disease.”