Effect of genetic variants associated with risk for inflammatory disease on immune cell phenotype and function

Summary

In the UK, at least 300,000 people have inflammatory bowel disease (IBD; which includes Crohn's disease and ulcerative colitis). IBD leads to chronic inflammation in parts of the digestive system and it is thought to occur due to an abnormal response to harmless bacteria in the gut. This response is believed to be a consequence of a complex interaction between environmental and genetic factors.
Our group and others have used genetic association studies (GWAS) to identify over 240 regions of the genome that increase susceptibility to IBD. Some of these regions are within well-known genes that interfere with the immunological response. However, most of them have no defined mechanism of action. Understanding how these variants contribute to someone developing IBD is important for our biological understanding of disease mechanisms and the development of novel therapies. In this project we aim to investigate the mechanisms by which four genetic variants increase the risk of developing IBD. These genetic variants are likely to play a role in the production and/or response to inflammatory mediators important in IBD. We will analyse changes in the gene expression and function of immune cells comparing individuals carrying the risk variants with those carrying the non-risk variants. Our studies aim to increase our understanding of how genetic variants affect the individual's immune function and might contribute to their increased risk for developing IBD.