Researchers say that genome-wide studies like theirs help scientists to better understand the biology of inflammatory bowel disease.
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.
People with IBD often experience diarrhea and pain, and they may pass blood from the rectum. Because the disease impairs the ability of the gut to absorb nutrients, it can also lead to anemia.
Estimates suggest between 1 million and 1.3 million people in the United States are living with IBD. In the U.K., where the studies took place, the disease affects more than 300,000 people.
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.
Gene variant doubles risk of ulcerative colitis
In one paper, the researchers describe how they found a rare variant of a gene called ADCY7 that doubles the risk of developing ulcerative colitis.
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 25 new genetic links to IBD risk. Some of the genes they identified could be targets of a class of drugs that is already showing results in treating IBD.
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.