The genetic basis of coeliac disease

DNA helixKnowing the genetic basis for coeliac disease is really important. It means we could potentially find new treatments for the condition and find out what the triggers for coeliac disease are. And if we know why people with the genes get coeliac disease, maybe one day we can stop it altogether. 

That's why we funded this research project with Professor David van Heel, a Professor of Genetics at The London School of Medicine and Dentistry, and consultant gastroenterologist at Barts Health NHS trust. David’s research interests include autoimmune diseases and the immunological consequences of disease predisposing genetic variants on human biology. Here we find out more about his research and what was achieved. 

What was the main issue your research was seeking to address?

We know from studies in families and in twins that coeliac disease has a strong genetic tendency, with close family members having a 10% chance of developing the disease themselves. We also know nearly all people with coeliac disease have HLA-DQ2/DQ8 type, but this type is also found in about third of healthy individuals. The HLA-DQ2/DQ8 type is therefore necessary but not sufficient to develop the disease. However the reason for this is not fully understood.  

What were you hoping to find out through this research? How successful were you?

We were hoping to reveal inherited factors which might explain why some people develop coeliac disease. We performed a study testing over 300,000 genetic variants in 778 individuals with coeliac disease and 1,422 without, which in total provided over 600 million measurements. We compared the frequency of each variant in people with and without coeliac disease.  

What are the key things that were learnt as a result of this project?

A small number of the 300,000 genetic variants are found to occur more commonly in coeliac disease, enabling us to find some of the genes that appear to be important. Our first finding was the interleukin-2 and interleukin-21 genes, these are important in determining how strong an immune response is made. We have found a further seven gene regions that might predispose to coeliac disease and we have now studied about 7,000 samples from the UK and Europe.      

How will this project benefit patients?

Having identified such gene regions that might predispose coeliac disease, we can study exactly how these gene variants cause coeliac disease. Understanding the ways in which genetic variants alter the immune system is important for finding new treatments.

Principle Investigator: Professor David van Heel

Institution: Barts and The London School of Medicine and Dentistry

Grant awarded: £300k