Global study identifies 47 genes related to ulcerative colitis

Forty-seven genes have now been identified that are associated with the chronic bowel disease ulcerative colitis. Dr Rinse Weersma, gastroenterologist at the UMCG, helped to coordinate a global study in which the results of six separate genome-wide association studies were combined and reanalysed. This resulted in 29 new genes being associated with ulcerative colitis. The findings were published in the journal Nature Genetics today. ‘These results provide increasing insight into how ulcerative colitis develops. This is a landmark study which will be referred to by everyone in coming years’, says Dr Weersma.

There is a strong collaboration in the Netherlands between all the university medical centres regarding research into ulcerative colitis (UC) and Crohn’s disease. This is part of the so-called ‘pearlstring’ (parelsnoer) initiative of the Ministry of Health, Welfare and Sport.

Both UC and Crohn’s disease are chronic inflammatory diseases of the gastrointestinal tract which are also known under the collective name inflammatory bowel disease (IBD). In the Netherlands there are some 90,000 patients afflicted by UC and Crohn’s disease. They often have to permanently use medication which acts on the immune system and many patients must also undergo operations. The UMCG has a multidisciplinary IBD centre which focuses on this group of young patients and their complicated problems.

Genome-wide study

Genetic research into IBD began at UMCG in 2000 and is part of a global IBD genetic research consortium in which numerous research groups from fifteen different countries participate. The technique used to identify the genes involved in UC was to analyse the complete genome of large groups of patients. The genome-wide data of 6,687 UC patients was compared with the data of 19,718 control patients in the meta-analysis. The findings from this group were then investigated in a second group of 9,628 UC patients and 12,917 control patients. The number of genes that are now associated with UC has been determined to be 47.

A similar metastudy for Crohn’s disease, which identified 71 genes, was also recently published in Nature Genetics. It was discovered that there are 19 genes that play a role in UC and in Crohn’s disease, which brings the number of genes associated with IBD to 99. For no other complex disease has such a great number of involved genes been established.

Genetic variants

The genetic map of UC is point of departure for research into the mechanisms underlying the disease’s origin. One of the main questions is how certain genetic variants influence the course of the disease. Another possibility is that due to these insights new or existing drugs can be tested for effectiveness in treating UC. In addition to research into the disease’s functional aspects, fundamental research into ulcerative colitis will also stand to benefit. The UMCG’s departments of Gastroenterology and Genetics are collaborating closely on this.

Dr Rinse Weersma received a rising star award in January 2011 from the United European Gastroenterology Federation for his research into the genetic foundation of IBD. The prize is awarded annually to the most promising gastroenterology researcher.