Abstract 14734: Circulating Sulfhydryl Oxidase and Risk of Cardiovascular Disease

Abstract

Introduction: Whether circulating quiescin sulfhydryl oxidase (QSOX) family enzymes level is causally associated with an increased risk of cardiovascular disease remains unestablished. In this study, we applied Mendelian randomization (MR) analysis to investigate the potential causal relationship between circulating QSOX family enzymes and a wide range of cardiovascular disease outcomes in European ancestry. Methods: Independent single nucleotide polymorphisms associated with QSOX1 and QSOX2 at the genome-wide significance level were selected as instrumental variables. Summary-level data for 9 cardiovascular endpoints were obtained from genetic consortia, the UK Biobank study, the FinnGen consortium, HERMES and MEGASTROKE. Results: Higher genetically predicted circulating QSOX2 levels were associated with an increased risk of coronary artery disease. For each standard deviation increase in genetically predicted QSOX2 levels, the odds ratio was 1.05 (95% confidence interval, 1.02, 1.07; p = 0.0001) for coronary artery disease. Significant causal association of genetically determined QSOX2 level with heart failure, ischemic stroke and peripheral artery disease was also found with the inverse-variance weighted MR method. However, no potential causal relationships between circulating QSOX2 and atrial fibrillation, intracerebral hemorrhage, pulmonary embolism, transient ischemic attack and venous thromboembolism were observed. There was no association between genetically predicted QSOX1 and cardiovascular disease. Conclusions: This study reveals suggestive evidence that lowering circulating QSOX2 levels may reduce the risk of coronary artery disease, heart failure, ischemic stroke and peripheral artery disease.