This thesis of Siqi Wang explores genetic insights into cardiovascular and kidney diseases, aiming to improve early diagnosis and treatment. It begins by analyzing genetic data with various methodological approaches to identify novel genetic variants and genes for the cardiac autonomic nervous system and to investigate the (causal) influence of this system on cardiovascular and kidney diseases.
A large exome-wide association study identified new genetic variants associated with resting heart rate and heart rate variability. Further analysis found causal links between the cardiac autonomic nervous system and disease related phenotypes, especially diastolic blood pressure. Genetic links between heart rate variability and hypertension were revealed, which suggested that lower heart rate variability increases hypertension risk.
A genome-wide association study of carotid intima-media thickness identified 25 novel loci linked to atherosclerosis. A further genome-wide association study highlighted genetic loci associated with kidney failure, suggesting distinct genetic components for kidney failure and function. The thesis also used genome and phenome data to explore the potential mechanisms and possibility of novel application of sodium-glucose cotransporter-2 inhibitors to cardiovascular and kidney diseases. Overall, this work offers significant genetic insights into cardiovascular and renal diseases and potential therapeutic targets.
