The human genome and microbiome in cardiometabolic disease Exploration through sequence-based technologies

In this thesis we used several different sequence-based technologies to explore the role of the human genome and microbiome in cardiometabolic disease. After introducing the cardiometabolic diseases that we investigated, as well as the human genome and microbiome and the methodologies that we applied in Chapter 1, we started off with studies focusing on the relationship between the human genome and cardiometabolic disease in part I. In Chapter 2, we studied the association between several genetic risk scores related to either development of type 1 diabetes, development of type 2 diabetes or C-peptide production and residual beta cell function and glycaemic control in type 1 diabetes patients. In Chapter 3, we identified new intronic variants in the LDLR gene and analysed if they could explain the FH phenotype in yet genetically undiagnosed patients. Thereafter, in part II, we dived into the relationship between the gut microbiome and cardiometabolic disease. In Chapter 4, we reviewed the existing literature on the interaction between medications prescribed for cardiometabolic disease and the gut microbiome. Additionally, we analysed the relationship between the gut microbiome composition and both metabolic syndrome (Chapter 5) and type 2 diabetes (Chapter 6) in a multi-ethnic cohort. Finally, the contribution of the human genome and microbiome were combined in part III, where we explored the role of gut microbial molecular mimicry in the autoimmune response to InsB9-23 of type 1 diabetes patients with a specific HLA-DQ8 genotype.