Genotype-phenotype relationships and their clinical implications in inflammatory bowel disease and type 2 diabetes

Complex diseases are caused and influenced by an interaction of genetic, environmental, and lifestyle factors. In recent years, methodological advances in genetic analysis have impressively expanded our knowledge of genetics. The most important applications of these advances are to understand the underlying mechanism of the diseases, and to develop predictive models that identify high-risk patients, by including previously unknown predictors. This thesis aimed to evaluate whether and to what extent genetic variants may influence and explain disease sub-phenotypes and complications of two complex diseases, namely inflammatory bowel disease (IBD), and type 2 diabetes (T2D). Accordingly, this thesis is divided into two parts. Part 1 is focused on the epidemiology of IBD, the role of genetic variants in disease phenotypes, and the prediction of the disease and Part 2 is focused on hyperglycemic control in T2D and the role of genetic variants in its disease complications.

We showed that genetic factors contribute to disease susceptibility in Asian populations (Chapter 3), and disease sub phenotypes (Chapter 4), while its predictive value is less apparent (Chapter 5) in IBD. Further, although several genetic variants are likely to contribute to complications of T2D, their identification remains difficult (Chapter 6). Finally, we found that long term anti-hyperglycemic therapy turned out to be sub-optimal, and a complete glycemic control is out of reach (Chapter 7).
It is now more important than ever to start incorporating genetic advances into routine clinical practice, to enable more personalized approaches to manage complex diseases such as IBD and T2D.