Leveraging Haplotype Diversity to Study Coronary Artery Disease Risk

At a Glance

This project aims to elucidate the function of a genetic risk factor for coronary artery disease (CAD), the leading cause of death in Wisconsin. Identifying molecular pathways driving CAD risk has the potential to inform actionable targets for preventive medicine and enhance health in the state and across the nation.

The Challenge

In Wisconsin, coronary artery disease (CAD) is the leading cause of death, with 13,000 deaths in 2021. While lifestyle choices and environmental factors contribute to CAD risk, genetics also play a substantial role, accounting for 40 to 60 percent of cases. Studies have identified approximately 200 specific genetic regions associated with susceptibility to the disease. One particularly important genetic region, known as 9p21.3, has been identified as a significant risk factor for CAD, yet its exact function remains unclear. Understanding how this genetic region works could lead to important insights for preventative medicine.

Project Goals

The overarching goal of this project is to advance the understanding of how genetic risk factors for CAD impact the function of vascular smooth muscle cells (VSMCs) and how genetic ancestry contributes to susceptibility. This goal will be addressed through three specific aims:

1. Determine the role of downstream effectors of 9p21.3 in driving cell state transition.
2. Assess causal variants in the 9p21.3 CAD locus driving the risk phenotype.
3. Build a platform to evaluate how CAD loci impacts VSMCs in different ancestries.