Genetics of complications in patients with type 2 diabetes

Abstract: Type 2 diabetes (T2D) is a polygenic disease caused by an interaction between genetic and environmental factors such as low physical activity, smoking, and obesity. The disease is associated with devastating chronic microvascular (nephropathy, retinopathy, and neuropathy) and macrovascular (coronary heart disease and stroke) complications. Genome-wide associated studies (GWASs) have been an unbiased and successful approach to identify genetic susceptibility loci for T2D. The overall aim of this thesis was to explore whether variants influencing T2D and/or cardiometabolic traits were also associated with an increased risk for diabetes complications. The additional aim was to investigate the effect of famine exposure and genetic susceptibility loci for the development of diabetes complications in patients with T2D from Ukraine, a population with a high risk for cardiovascular diseases. Results from the present studies suggested shared genetic susceptibility between T2D and the development of diabetes complications for a number of loci including variants in the HMGA2, KCNJ11, and GIPR. Furthermore, our results suggest that the link between famine exposure and diabetes complications may involve genomic regions regulating immune response (PIK3GC), nutrient sensing (PPARG), stress (ADRA2A), imprinting (KCNQ1), and organ development (HNF1A, ELMO1, DYNQL11). In summary, studies presented in this thesis provide an important contribution to the field of genetics of diabetes and its complications.