Looking at genetic variations that cause IBD



By uncovering exactly how genetic variants contribute to Crohn's disease and ulcerative colitis, we aim to identify previously unknown pathways that are involved in disease development, which could provide new targets for better treatments.

Dr James Lee
University of Cambridge 

What is this research looking at? 

Differences between individuals such as eye colour, hair colour and height are due to tiny parts of DNA that vary between people. Similar genetic variations in DNA have been a major focus of Inflammatory Bowel Disease (IBD) research for more than 10 years, as some of them affect your chance of developing Crohns Disease or Ulcerative Colitis (UC).  Scientists realised some time ago that if they could identify the particular genetic variations that contribute to IBD, they could probably learn more about what causes IBD to develop, and therefore discover better treatments. 

More than 200 genetic variations have been found that affect your risk of developing Crohn’s or UC.  However, scientists have been unable to figure out what these variations do, or why they contribute to someone developing Crohn’s or UC.  The studies are very difficult, and until recently researchers could only study one genetic variation at a time, making this type of research very slow. 

Now, a technique developed at Harvard University allows researchers to work out the function of multiple pieces of DNA at the same time, including the effects of any genetic variations within these pieces of DNA.  The scientist leading this study has spent the last 2 years at Harvard learning this technique, so he can use it to discover how genetic variations associated with IBD can contribute to developing the disease.  The researchers will investigate five sections of DNA that have been liked to IBD, as well as other diseases including rheumatoid arthritis and coeliac disease.  They hope to discover the pathways inside the body that are disrupted by each genetic variation, so they can better understand what goes wrong when IBD develops, and hopefully identify new targets for treatments.     

What do researchers think this could mean for people with IBD? 

The researchers aim to identify key pathways in the body involved in the development of IBD. They hope this leads to the discovery of better treatments that can target these specific pathways, which might also be useful for people with other autoimmune diseases. This will improve upon current treatments that are often less targeted, and can produce unwanted side effects.  

Who is leading this research:  Dr James Lee, University of Cambridge 
Our Funding: £87,463 
Duration: 24 months 
Official title of application: From genetic variants to a better understanding of IBD susceptibility – functional characterisation of non-coding GWAS hits