Sudden cardiac arrest (SCA) is a major cause of cardiac mortality, affecting over 300,000 people in the US every year. While clinical and autopsy studies have demonstrated a predominant, common pathophysiology in Western populations - the most common electrophysiologic mechanism for SCA is ventricular fibrillation (VF) and the most common pathologic substrate is coronary artery disease (CAD) ' much remains unknown about cardiac arrest etiology. Moreover, studies suggest that the underlying etiology of sudden death differs between men and women. Although observational studies have identified numerous clinical and subclinical risk factors for SCA, understanding which of these associations are causal will help target prevention strategies. Genome-wide association studies (GWAS) have proven to be a powerful tool to examine the genetic architecture of common complex diseases, including SCA. This proposal will perform the largest GWAS of SCA in order to achieve the following specific aims: (1) We will use GWAS to identify novel variants, genes, and processes associated with SCA. (2) Using Mendelian Randomization methodology, we will identify sex-specific effects of (a) traditional risk factors and (b) novel risk factors for SCA. This will allow us to find both novel risk factors, as well as explore potentially causative processes. Finally, we will determine whether a polygenic risk score will help identify individuals at high risk of sudden death, particularly among those at already elevated risk due to inherited or acquired factors. The ultimate goal is to use genomic and precision medicine methods to better target treatment and prevention strategies.
|Program type||Strategically Focused Research Network|
|Effective start/end date||07/01/2019 → 06/30/2023|