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Genetic susceptibility for inflammatory bowel disease across ethnicities and diseases

PhD ceremony:Ms S. (Suzanne) van Sommeren
When:November 25, 2019
Supervisors:prof. dr. R.K. (Rinse) Weersma, prof. dr. C. (Cisca) Wijmenga
Where:Academy building RUG
Faculty:Medical Sciences / UMCG
Genetic susceptibility for inflammatory bowel disease across
ethnicities and diseases

The inflammatory bowel diseases (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), have a broad disease spectrum and disease course and response to therapy are unpredictable. We need to understand the aetiology and the influence of genetic risk factors. This thesis contributes to this by identifying 38 new genetic risk factors. We show that the majority of genetic risk factors are shared between populations. A small proportion differs between populations, possibly environmental factors underlie this. Furthermore we replicated a few UC associated loci, which encode genes with functions in the intestinal barrier. We also developed a method to select genetic risk factors based on their relationship with gene expression, hypothesis that these represent biologically relevant signals. In this way we identified 2 new CD loci.In order to make a translation to biologically relevant processes we investigated the influence of genetic risk factors on gene expression in the Th17/IL23 pathway, a pathway that is important in IBD pathogenesis. We didn’t find a correlation and we expect this is due to the fact that gene expression is cell specific and we used a mix of cells. Lastly, we investigated the overlap in genetic risk factors between IBD and a group of diseases that occur often with IBD: the extra-intestinal manifestations and with a disease that occurs after allogeneic cell transplantation and resembles CD: gastro-intestinal graft-.vs.-host disease. We find substantial overlap, not only based on genetic factors, but also based on co-expression of genes and protein-protein interaction.