Cardiorenal events are the leading cause of mortality worldwide, particularly in people with diabetes. Diabetes is a complex and heterogeneous disorder, characterized by diverse pathogenic backgrounds, clinical outcomes and response to treatment. Although several risk factors and genetic contributors are already known, how they interact each other to shape the risk of both cardiorenal events and mortality remains unclear. Large studies exploring how these markers interact across different groups and how heterogeneity outcomes arise from genetic background and environmental exposures are limited, since integrating heterogeneous datasets, and ensuring consistent long-term follow up across cohorts is challenging.
The UK-Biobank with deep genomic data, detailed phenotyping and lifestyle assessments provides a unique framework to address these gaps.
Our aim is to investigate how heterogeneity, arising from genetic and non-genetic (environmental, phenotypical and behavioral) factors, influences the risk of death and cardiorenal events in individuals with diabetes compared to the general population, using comprehensive UK Biobank data.
Specific aims are:
1: to investigate the incidence of major cardiorenal events and all-cause mortality in individuals without and with diabetes;
2: to address whether different risk levels of cardiorenal events and/or mortality in people without and with diabetes are associated with genetic and non-genetic factors that can be, therefore, used as prediction markers.
3: to evaluate if and how non-genetic factors mediate genetic effects on cardiorenal events and mortality.
Pursuing these aims will support personalized risk stratification, identify drivers of inter!individual variability, and clarify pathways shaping risk profiles, thus paving the way for precision medicine in terms of prediction, prevention, diagnosis and treatment.
