Celiac disease is the most prevalent food intolerance known. Individuals suffering from celiac disease develop a severe intestinal inflammation in response to gluten proteins that are present in the grains that form the basis of the Western diet. Although the incidence of celiac disease is 1%, it is thought that only 1 in 8 celiac patients is, in fact, diagnosed correctly. The only treatment for celiac disease is a life-long, gluten-free diet. Compliance is difficult and significantly affects the patient’s overall quality of life. This all means there is an urgent need to gain a better understanding of celiac disease and its mechanisms, which we hope will lead to the development of better diagnostic tools and/or treatment options.
Recent studies have identified 40 regions in the human genome that predispose to the development of celiac disease. In this thesis, I applied statistical genetics and pathway analysis methods to gain a better understanding of how the predisposing genetic factors contribute to celiac disease. I prioritize functional variants, genes and pathways affected in celiac disease, including a long non-coding RNA that is regulated by a celiac-associated genetic variant.
An exciting development is that circulating micro-RNA molecules have been identified as a new class of biomarkers for immune-mediated diseases. I found microRNAs candidates that can be used as novel biomarkers for celiac disease development and to monitor a patient’s adherence to the gluten-free diet. These biomarkers can be developed into useful clinical tests.