Endometriosis and the Risk of Cardiovascular Diseases: A Mendelian Randomization Study

Abstract

Abstract Background Observational studies have shown associations between endometriosis and cardiovascular disease (CVD). But residual confounding and the potential for reverse causality are inevitable in such routine observational studies. This study used Mendelian randomization (MR) design to evaluate the causal effect of endometriosis on CVD including coronary heart disease (CHD), myocardial infarction (MI), atrial fibrillation (AF), heart failure (HF), hypertension and Stroke. Methods We utilized publicly available summary statistics of genome-wide association studies (GWAS) from European participants in the UK Biobank and Finnish databases. Instrumental variables (IVs) associated with endometriosis and CVD were identified and used IVs to investigate the genetic causal relationship between them. MR analyses were performed using various analytical methods, including Inverse variance weighted (IVW), MR-Egger, and Weighted Median. Tests for pleiotropy and heterogeneity were performed to assess the reliability of causality. Results MR analysis showed that endometriosis was associated with hypertension (odds ratio (OR) = 0.9990, 95% confidence interval (CI) : 0.9981–0.9998, P = 0.0191), which may be a protective factor. However, this significance disappeared after applying the Bonferroni correction. Endometriosis was identified as a risk factor for CHD (OR = 1.0025,95%CI: 1.0005–1.0046, P = 0.0164), but this significance was lost after Bonferroni correction. Endometriosis was identified as a risk factor for MI (OR = 1.0018, 95%CI: 1.0005–1.0032, P = 0.0058), which remained significant after Bonferroni correction. Genetic associations between endometriosis and other CVD were not significant. Conclusions MR studies have shown that genetic predisposition to endometriosis is significantly associated with the risk of myocardial infarction, and may be associated with the risk of CHD and hypertension. However, the causal relationships between endometriosis and AF, HF and Stroke need to be further explored.