Type 1 diabetes and Crohn's disease genes identified

A major collaboration of UK scientists has provided an insight into the genetics underlying a number of diseases including Crohn's disease, a type of inflammatory bowel disease, and type 1 diabetes. The Crohn's and type 1 research, led by Cambridge University scientists, has identified for the first time a gene linking these two autoimmune diseases.

The studies were part of the Wellcome Trust Case Control Consortium (WTCCC), the largest ever study of the genetics behind common diseases including type 2 diabetes, coronary artery disease and bipolar disorder.

Researchers initially sampled 2,000 patients with each disease and 3,000 healthy individuals. In order to confirm the findings, they then studied a further 17,000 people with and without type 1 diabetes and 1,180 people with Crohn's. Their findings are published today in the journal Nature Genetics to complement the main WTCCC study in Nature.

Important mechanism identified for Crohn's disease

The study of Crohn's disease, led by Dr Miles Parkes from the University of Cambridge and Addenbrooke's Hospital, has identified three new genes that increase the risk of developing the disease plus a region containing several genes and a so-called "gene desert", which all appear to be involved. It has also confirmed the importance of a process known as autophagy. Autophagy, or "self eating", is a process responsible for clearing unwanted material, such as bacteria, from within cells, highlighting the central importance of this pathway in the interaction of gut bacteria in health and in inflammatory bowel disease.

"The study has substantially advanced our understanding of what causes Crohn's disease," says Dr Parkes. "Although there is a lot of follow-up work required to fully understand how the genetic associations that we have identified cause chronic bowel inflammation, a number of mechanisms have been highlighted. In particular, abnormalities in the autophagy pathway clearly correlate with susceptibility to Crohn's disease. These findings have already provided some major leads regarding possible new treatment options. Although further careful evaluation is required it would be a great result if the genetic knowledge leads directly to clinical benefit for our patients."

Richard Driscoll, Director, National Association for Colitis and Crohn's Disease, which helped fund sample collection from patients, says: "People who have Crohn's Disease are often diagnosed at a young age and have to live with the distressing and painful symptoms for the remainder of their lives. These new genetic findings will encourage everyone that real progress is at last being made in understanding how Crohn's develops. With a greater understanding we are that much closer to being able to give people a more accurate prognosis of how their illness may develop and which treatments may work best for them."

Type 1 diabetes and Crohn's disease link identified

Researchers including Professor John Todd from the University of Cambridge identified four confirmed new chromosome regions and two further possible regions that increase the risk of developing type 1 diabetes. Moreover, the WTCCC indicated the involvement of a common gene in the two diseases. The gene, PTPN2, is involved in regulating the immune system, and was confirmed by both the subsequent disease-specific studies in Crohn's disease and in type 1 diabetes. It leads to the production of a phosphatase enzyme, which regulates signals into and out of cells.

"We now have confirmation that there are at least 10 genes that increase on average a person's chances of developing type 1 diabetes," says Professor Todd. "We know that the causes of diabetes are complex and that the genes almost certainly interact with environmental factors, such as diet, low levels of vitamin D and viral infections, to cause the disease. But this is the first time that we have seen a link between type 1 diabetes and Crohn's disease."

"The link between the two diseases is a promising avenue for us to understand how they occur. The pathways that lead to Crohn's disease are increasingly well understood, particularly when enhanced by these new findings. We hope that progress in treating Crohn's disease may give us clues on how to treat type 1 diabetes in the future."

The findings have been welcomed by Karen Addington, CEO of Juvenile Diabetes Research Foundation (JDRF) in the UK. JDRF jointly funded the study of people with type 1 diabetes with the Wellcome Trust.

"This study is a landmark in the field of diabetes research," says Ms Addington. "For the first time we can pinpoint which genes increase the likelihood of developing type 1 diabetes across the entire human genome. The more that we understand how and why the condition occurs, the closer we come to being able to prevent and cure it."

Largest ever study of the genetics of disease

The £9 million WTCCC has been one of the UK's largest and most successful academic collaborations to date, involving 50 leading research groups in the field of human genetics from dozens of institutions.

Of the over 200 scientists involved in the project, a significant number were from the University of Cambridge, including Dr Willem Ouwehand at the Department of Haematology who led the team which collected and processed 3600 samples to establish one of the common control collections used for the study.