Genetic Clue to Treating Irritable Bowel Syndrome

By Jane Farrell

Genetics researchers in the UK have identified a genetic variant that doubles an individual’s risk of developing ulcerative colitis, one of the subtypes of a chronic disorder known as Inflammatory Bowel Disease (IBD).

The investigators, from the Wellcome Trust Sanger Institute and other centers, also uncovered a further 25 novel genetic associations to IBD risk. Several of these genes may be related to drugs that have shown promise in the treatment of this disease.

More than 300,000 people suffer from IBD in the UK. The disorder primarily consists of two subtypes: ulcerative colitis and Crohn’s disease, neither of which currently have a cure. IBD is a debilitating disease in which the body’s own immune system attacks parts of the digestive tract. The exact causes of this disease are unclear.

To understand more about the genetics underlying IBD, researchers studied the genomes of 16,000 UK IBD patients, as well as 10,000 more from a previously published international study, in the largest whole-genome IBD genetic study to date.

From the research, which included 5 per cent of IBD sufferers nationwide, scientists identified a rare genetic variant that doubles the risk of ulcerative colitis. The variant affects a gene known as ADCY7, and is carried by 1 in 200 people in the UK. It is one of the strongest genetic risk factors associated with ulcerative colitis to date and presents a novel drug target for IBD.

In the second study, researchers identified that a family of proteins called integrins play a key role in increasing the risk of IBD. Integrins are transmembrane proteins that act as bridges for interactions between cells from the immune system and the rest of the body. For the inflammation associated with IBD symptoms, drugs targeting some of these interactions have been shown to be effective. This study demonstrated that genetic variants that increase the risk of developing IBD also increase the expression of certain integrins in response to stimulation of the immune system.

These examples of genome wide association studies give scientists a clearer view of IBD biology than they had previously and are helping to reveal the underpinning biology of human inflammatory diseases overall.

Sanger Institute scientists, with help from the UK IBD BioResource, are aiming to sequence 25,000 genomes of IBD patients in the next five years. The unprecedented scale of this study will hopefully reveal even more details of the biology of this condition.

The results from these studies will be translated into potential treatments by Open Targets, an initiative that takes the outputs of the genetic studies and works with pharmaceutical companies to aid the development of new treatments for diseases, including IBD.