Glaucoma and cardiovascular disease: a bidirectional two-sample Mendelian randomization analysis

Many studies reported that glaucoma is associated with cardiovascular disease (CVD). This study aims to investigate the potential causal relationship between glaucoma and CVD using a bidirectional two-sample Mendelian randomization (MR) analysis. The genome-wide association studies (GWAS) of glaucoma and CVD were downloaded from the IEU OpenGWAS project. The CVD included unstable angina pectoris (UAP), coronary artery disease (CAD), high blood pressure (HBP), myocardial infarct (MI), heart failure (HF), ischemic stroke (IS), atrial fibrillation (AF), and pulmonary embolism (PE). The inverse variance weighting (IVW) analysis was the primary method in MR analysis. Meanwhile, sensitivity analysis and statistical power tests were performed. The random effects IVW method showed a causal relationship between glaucoma and a decreased risk of MI (Odds ratio (OR): 0.94, 95% confidence interval (CI): 0.89-0.99; P = 0.012). In the reverse MR analysis, genetic susceptibility of UAP (OR: 1.12, 95% CI: 1.02-1.23; P = 0.022), CAD (OR: 1.1, 95% CI: 1-1.21; P = 0.041), and HBP (OR: 1.83, 95% CI: 1.25-2.67; P = 0.002) was significantly linked to an increased risk of glaucoma. MR-Egger (P = 0.005) and IVW (P = 0.005) methods found that HBP presented different degrees of heterogeneity. The random effects IVW method also demonstrated that HBP is the risk factor for glaucoma (P = 0.0017). Although reverse MR initially suggested a potential association between CAD and glaucoma, MVMR showed no causal relationship after adjusting for obesity and BMI. The MR analysis found that glaucoma serves as a protective factor for MI, while UAP and HBP were risk factors for glaucoma in the European population, which may contribute to preventing and managing glaucoma and CVD.