Abstract
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.
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.
| Translated title of the contribution | De volgende stap na genoom-wijde associatie studies: de rol van het niet-coderende genoom |
|---|---|
| Original language | English |
| Qualification | Doctor of Philosophy |
| Awarding Institution |
|
| Supervisors/Advisors |
|
| Award date | 25-Mar-2015 |
| Place of Publication | [S.l.] |
| Publisher | |
| Print ISBNs | 978-90-367-7718-6 |
| Electronic ISBNs | 978-90-367-7760-5 |
| Publication status | Published - 2015 |