Phd ceremony Ms. K. Fransen: Inflammatory bowel disease. The genetic background and beyond

Inflammatory bowel diseases (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC) are partially heritable and partially environmentally determined diseases that are characterized by a chronically relapsing inflammation of the gut. Probably an aberrant immune response to commensal microflora of the bowel, together with a diminished integrity of the wall, is culprit to these serious diseases. More insight into their pathogenesis is essential.

Screening the DNA for risk areas, has up to now revealed 163 areas that are associated with increased disease risk, and can explain 15-25% of the heritability. In this thesis we investigated a number of potential sources of the hidden heritability. Possibly there are more risk areas for IBD. We analyzed a number of strategically selected areas and identified two new risk areas for IBD. In another study we found an altered risk for a UC and CD gene. Also, a larger part of the heritability might be explained by the known risk areas. In theory, the same genetic code may has a different effect to disease risk when inherited from the father or the mother. We tested overlapping IBD risk areas and found limited evidence for such effects.

Furthermore we investigated the effects of a number of risk areas on a cellular level in immune cells. We could not find such a relation, although we did find a difference between healthy individuals and patients.In conclusion, we contributed to the identification of new risk areas on the DNA for IBD and investigated other potential sources for the hidden heritability.