Large-scale integrative molecular studies of CVDs in multi-ethnic cohorts

Researchers will sequence the genomes of thousands of people who developed heart disease unusually young, then track the molecular chain of events—from RNA to proteins to metabolites—that leads from a genetic variant to a blocked artery. Heart disease remains the world’s leading cause of death, yet most treatments target the same few pathways. Many drugs that work in theory fail in trials because the underlying biology is poorly understood. This project tackles that gap by treating the human genome as a natural experiment. By identifying people who carry naturally occurring “knockouts”—mutations that disable a gene without causing disease—the team can predict which drug targets are likely to be safe and effective before a single molecule is synthesised. If successful, this work could shift cardiovascular drug development from trial-and-error to a genetics-first pipeline. The same Mendelian randomisation framework used here to prioritise targets could also be applied to other common diseases, reducing the cost and failure rate of clinical trials. This is fundamental science with a clear translational route: understanding the causal chain from DNA to disease, rather than just statistical associations, is what makes a drug target worth betting on.