There’s a critical gap in cardiovascular health: patients regularly have heart attacks or strokes despite receiving treatments to lower their cholesterol and blood pressure.
Wei-Qi Wei, MD, PhD, associate professor of Biomedical Informatics at Vanderbilt University Medical Center, has been awarded a four-year, $3.4 million research grant from the National Institutes of Health to study this residual risk of atherosclerotic cardiovascular disease (ASCVD) and identify any existing drugs that might help lower this risk.
“Our goal is to uncover the underlying mechanisms of residual ASCVD risk, identify patients at higher risk, and explore new treatment options,” Wei said. “By leveraging advanced genetic and data science techniques, we hope to make significant strides in reducing the burden of cardiovascular disease.”
The project will begin with Vanderbilt’s DNA biobank, BioVU, where a genome-wide association study (GWAS) will compare patients who do, and do not, experience ASCVD events while on preventive treatment. The team will meanwhile conduct machine learning on electronic health records (EHR) to predict residual ASCVD risk.
These initial steps will produce polygenic risk scores for residual risk and better automated EHR risk stratification, with results subject to validation in two national biobanks, eMERGE and All of Us.
Genetic risk variants found in GWAS will also be used to impute the transcriptome and overall gene expression pattern characteristic of residual ASCVD risk. These data, combined with a method called Mendelian randomization, will power an efficient search for drug repurposing candidates, with results again to be validated using national patient databases.
Wei is scientific director for the phenotyping core at VUMC’s Center for Precision Medicine. Some of the concepts and methods driving this new project have been pioneered and refined by Wei and his team.
Co-leading the effort with Wei will be Qiping Feng, PhD, associate professor of Medicine in the Division of Clinical Pharmacology. Others on the project include Quinn Wells, MD, PharmD, MSCI, MSc,
Jonathan Schildcrout, PhD, Nancy Cox, PhD, Mike Stein, MBChB, and Ran Tao, PhD. The project is supported by NIH grant R01HL171809.
