Celiac disease is a common autoimmune disorder affecting at least 1-3% of the Western population. It belongs to the same group of complex disorders as rheumatoid arthritis and multiple sclerosis that is characterized by multiple genetic and environmental factors playing a role in the disease development. Celiac disease is the result of an inflammatory response in the small intestine. This is triggered by dietary gluten, which comes from grain (wheat, barley, rye) proteins abundantly present in the Western diet. The damage caused by the inflammation leads to malnutrition and a wide variety of symptoms like abdominal pain, chronic diarrhea and anemia. So far, the only effective treatment for celiac disease is a life-long gluten-free diet.
The aim of my thesis project was to identify novel genetic factors predisposing to celiac disease and to investigate how they might contribute to the disease mechanism. In my thesis I describe novel genetic variants that were identified by looking at the more extreme phenotypes and/or by following-up suggestively associated GWAS variants by increasing the sample size. My results indicate that long non-coding RNAs (lncRNAs), which are a new class of RNA molecules, might be important players in the pathophysiology of celiac disease. The prediction methods I applied in this work can also be used to prioritize interesting cell types for functional studies with these long non-coding RNAs.