This protocol supports broad research examining the genetic and epidemiologic determinants of cardiovascular, cardiometabolic, and related conditions using UK Biobank data. All analyses will be conducted at Massachusetts General Hospital and the Broad Institute of MIT and Harvard. Coronary artery disease (CAD) remains a major global cause of mortality. Although lowering low-density lipoprotein (LDL) cholesterol reduces risk, substantial residual risk persists, underscoring the need to uncover additional biological contributors and preventive approaches. Within this protocol, we will apply genomic and epidemiologic methods to identify novel genetic factors underlying cardiovascular, cardiometabolic, and related disorders-including clonal hematopoiesis of indeterminate potential (CHIP) and hypertensive diseases-inform prevention, and highlight potential therapeutic targets. Planned areas of investigation include:
Modifiable cardiovascular disease risk factors
Causal biomarkers and biological pathways relevant to CAD, heart failure, valvular heart disease, and cardiac arrhythmias
Sex-specific genomic analyses of cardiometabolic traits and outcomes
Long-term variability of lipoprotein(a) and its relationship to cardiovascular risk
Genetic determinants of lipid metabolism
Genomics of hypertensive disorders of pregnancy
Associations between cardiometabolic risk factors, pulmonary hypertension, and disease progression
Distribution and clinical relevance of CHIP-associated mutations in atherosclerotic disease
Impact of clonal hematopoiesis on peripheral artery dise