Cardiovascular disease remains a leading cause of morbidity and mortality globally, accounting for an estimated 17.9 million deaths annually. It encompasses a spectrum of arterial pathologies, including coronary artery disease, myocardial infarction, and stroke, with complex interactions between genetic predisposition and environmental risk factors. Chronic venous disease (CVD), including varicose veins, deep vein thrombosis, and venous leg ulcers, affects up to 25-40% of the adult population globally. Although traditionally considered separate, emerging evidence suggests shared vascular risk determinants between cardiovascular disease and CVD – for example, a recent review showed patients with higher CEAP classes to be associated with a higher 10-year risk for cardiovascular disease development.
Both arterial and venous disorders involve key processes such as endothelial dysfunction, vascular remodelling, extracellular matrix dysregulation, inflammation, and altered haemodynamics. These mechanisms are influenced by genetic variation affecting vascular wall structure, thrombosis pathways, and inflammatory signalling. For instance, loci in genes regulating extracellular matrix integrity (e.g., COL3A1, ELN) and vascular tone (e.g., NOS3) have been implicated in both arterial stiffness and venous dilation. However, these findings have mostly arisen from separate studies with limited power to detect cross-disease effects.
This project therefore aims to investigate the genetic overlap between cardiovascular disease and CVD. The primary research questions are:
1. What genetic variants are associated with cardiovascular disease and CVD in the UK Biobank population?
2. To what extent do these two conditions share common genetic risk loci?
3. Are the shared loci enriched in particular biological pathways or tissue types?