Approved Research

The role of rare genetic variants in coronary artery disease and related risk factors

Lay summary

Coronary artery disease (CAD) is a tremendous public health burden. While many studies to date have evaluated and proved that genetics play in important role in the onset and progression of CAD, these studies have been limited to common genetic variants, or genetic variants in coding regions of the genome. Research suggests that low-frequency and rare genetic variants play an important role in understanding the heritability of CAD and regulation of genes that influence the risk of CAD and related CAD traits. As whole genome sequencing (WGS) data becomes more widely available, the ability to study the role of these variants is become increasingly important. Our goal is to evaluate the role of rare genetic variants in association with CAD and CAD related traits, specifically evaluating their potential to improve current genetic prediction methods such as polygenic risk scores. Over the course of a 2 year period, we plan to leverage UK Biobank WGS sequencing data to develop these scores, in conjunction with the data available through National Heart Lung and Blood institute  Trans-Omics in Precision Medicine (TOPMed) program, to provide unprecedent insight into the role of rare genetic variants in the prediction of CAD. Finding ways to improve polygenic risk prediction through the incorporation of rare genetic information, expands the genetic risk information that can be communicated to the general population. Thus, the findings from this study could be used to implement effective, personalized lifestyle and medical interventions to offset the risk and delay or prevent disease onset and ultimately reduce the global burden CAD.