Abstract 12097: Genetics of Cardiac Troponin

Abstract

Introduction: In the absence of coronary artery disease, observational studies suggest that myocardial injury may occurs because of drugs/toxins, infection, inflammatory disease, and malignancy, alongside commonly associated conditions such as heart failure, kidney disease, and hypertension, among others. The causes and optimal treatment for myocardial injury without ischemic heart disease remains an unmet need in cardiovascular medicine. We aimed to leverage genome-wide association studies (GWAS) to identify previously unreported risk loci for circulating troponin levels in the absence of ischemia, and Mendelian randomization (MR) to highlight causes of myocardial injury and identify potential targets for intervention. Methods: We performed a GWAS meta-analysis of circulating cardiac troponin I (cTnI) and T (cTnT) among up to 46,267 healthy ambulatory individuals using METAL. Using publicly-available GWAS of ~40 common cardiovascular risk factors such as lipids, blood pressure, and kidney function available from the IEU Open GWAS Project, we used Mendelian randomization (MR) to identify their potential causal association with circulating troponin. We primarily employed inverse-variance weighted MR; weighted median and weighted mode methods were applied as sensitivity analyses. Results: Our meta-analysis revealed three risk loci each for cTnI and cTnT, including a previously unreported signal on chromosome 3 (rs1706435) for cTnT. After accounting for multiple testing by controlling the false discovery rate (q < 0.05), MR identified 8 and 10 cardiovascular risk factors associated with elevated cTnI and cTnT, respectively. These factors included blood pressure, creatinine, classes of obesity, and waist circumference. Conclusions: This analysis identified a new risk locus for circulating troponin in the absence of ischemia. Our MR results provide human genetic evidence to support obesity and hypertension as important contributors to elevated circulating troponin, highlighting their potential role in myocardial injury.