Published: 01-11-2012 00:00 | Updated: 08-06-2015 14:17

Genetics of infection at the basis of inflammatory bowel disease

In one of the largest studies of its kind, an international team of scientists, including researchers from Karolinska Institutet, has identified 71 new genomic regions that predispose to inflammatory bowel disease (IBD). The results, which are presented in the scientific journal Nature, also provide evidence that immune responses to bacterial infection may have shaped IBD genetics throughout evolution.

The present study is based on a so called meta-analysis of 15 previous genome-wide association studies combined, and includes more than 75000 IBD patients and controls from around the world. The researchers were able to identify 71 new regions of the genome that predispose to IBD, increasing the total number of risk genes to 163 – far more than reported for any other complex disease.

"Not only is there a remarkable genetic overlap between Crohn's disease and ulcerative colitis, the two subtypes of IBD", says Docent Mauro D'Amato, who led the Swedish part of the investigation. "But 70 per cent of their predisposing genes are also common to other complex inflammatory diseases, particularly psoriasis and ankylosing spondylitis, which tells us they share key biological pathways".

A closer look at the identified genomic regions reinforced the idea that IBD results from exaggerated responses to bacteria, and that the causative genes have evolved through a delicate equilibrium between fighting infections and inducing harmful excessive inflammation.

"The fact that several regions identified in this study have also been previously associated to susceptibility to mycobacterial infections, such as leprosy and tuberculosis, underscores the essential role of host defenses against infection and paves the ground for new lines of investigation in IBD", says Mauro D'Amato.

Crohn's disease and ulcerative colitis affect approximately 2.5 million people in the western world, and are alarmingly increasing among teenagers. In Sweden 0.5 - 1 per cent of the population develop these diseases, which manifest as chronic inflammation of the gastrointestinal tract.

"We are talking about lifelong illnesses marked by periods of relapse and remission, with symptoms including diarrhea, abdominal pain, rectal bleeding, debility, and a decrease of life quality in general", says Docent Leif Törkvist, Senior Consultant at the Gastro Center of Karolinska University Hospital in Stockholm. "There is currently no cure, and surgery to remove damaged intestinal tissue is often necessary."

The study stems from large collaborative efforts within the International IBD Genetics Consortium (IIBDGC), a worldwide network of researchers working on the genetics of inflammatory bowel disease in the hope that their research findings can be translated into improved diagnoses and treatment. Study leaders were Dr Jeffrey C Barrett at the Wellcome Trust Sanger Institute in the UK, and Dr Judy H Cho from the Yale School of Medicine, US.


Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
Jostins L, Ripke S, Weersma R, Duerr R, McGovern D, Hui K, et al
Nature 2012 Nov;491(7422):119-24