Sophie de Ruiter

Multi-omics data integration and sex-specific analysis to improve the understanding of cardiovascular disease

Samenvatting

Cardiovascular disease (CVD) remains a leading cause of death. Observational studies suggest some risk factors, such as smoking and type 2 diabetes, are more strongly linked to CVD in women, but whether this reflects sex differences in causal effects is unclear. This thesis applies Mendelian randomisation (MR) to study this. We show smoking and diabetes have broadly similar causal effects in both sexes. Integrating multi-omics data, including proteins, metabolites, and plaque tissue, we uncover causal pathways and druggable targets for atrial fibrillation, heart failure, cardiomyopathies, and coronary disease. We conclude that sex-specific MR combined with omics integration can unravel CVD biology and inform improved therapies.