A large body of genetic research, published as two studies, promises to improve scientists’ understanding of the biology of inflammatory bowel disease and offers potential new drug targets. One study identifies 25 new genetic links to the digestive disease, while the other identifies a gene variant that doubles the risk of ulcerative colitis, a type of inflammatory bowel disease that leads to ulcers in the inner lining of the large intestine.
Both studies – led by the Wellcome Trust Sanger Institute at Hinxton in the United Kingdom – are published in the journal Nature Genetics.
Inflammatory bowel disease (IBD) is a group of chronic disorders that cause inflammation of the gut or gastrointestinal (GI) tract. There are two main types of IBD: ulcerative colitis and Crohn’s disease, neither of which is currently curable.
Although the exact causes are unknown, scientists suspect that IBD is an autoimmune disorder that arises when the body’s own immune system mistakenly attacks tissue of the GI tract.
Across the two studies, the researchers analyzed the genomes of more than 16,000 patients with IBD in the U.K. They also included the results from a previously published international genome study of more than 10,000 other people with IBD. The research is the largest whole-genome study of IBD to date.
In one paper, the researchers
The variant, which is carried by 1 in 200 people in the U.K., is one of the strongest risk factors for ulcerative colitis discovered so far. The researchers suggest that it offers a potential target for new IBD drugs.
In the other study, the researchers identified another
The investigators found that a family of transmembrane proteins called integrins plays an important role in raising the risk of IBD.
Integrins are the main link between cells and their environment, and act as bridges for interactions with the immune system and the rest of the body.
Some of these interactions have already been identified as drug targets for reducing inflammation associated with IBD symptoms.
Researchers also discovered that some of the genetic variants linked to higher risk of IBD can also raise expression of certain integrins when stimulated by the immune system.
The team says that genome-wide studies such as these help scientists to better understand the biology of IBD, as well as other human inflammatory diseases, more clearly.
Over the next 5 years, and with help from the IBD BioResource, the researchers plan to sequence the genomes of 25,000 patients with IBD and discover more about the biology of the disease.
“We study genetics because we ultimately want to understand the biology of the disease. From the genetic information we can extract a compelling story about why a particular anti-integrin drug is effective against inflammatory bowel disease, or why others have serious side effects.”
First author Katrina de Lange, Wellcome Trust Sanger Institute