Abstract 16539: Endometriosis Does Not Have a Causal Role in Determining Cardiovascular Disease and Cardiac Structure and Function: Evidence From Mendelian Randomization

Introduction: Previous observational studies have suggested an association between endometriosis and higher risk of cardiovascular disease. However, in the observational setting residual confounding could drive the association. Hypothesis: In this study, we hypothesize that endometriosis might be causally related to cardiac disease, structure and function, and investigate this using Mendelian randomization (MR), a method that is not liable to influence by observational confounding. Methods: Genome-wide significant (p<5x10-8) uncorrelated (r2<0.001) variants associated with endometriosis in a recent genome-wide association study of 60,674 cases and 701,926 controls were extracted as instrumental variants. Gene-outcome association data was extracted from GWAS of atrial fibrillation, coronary artery disease, heart failure, ischaemic stroke, and 15 different indexed cardiac magnetic resonance markers of structure and function. Inverse-variance weighted MR was used for primary analysis. A further exploratory analysis was performed for the outcome of atrial fibrillation, extracting data from a different GWAS study, to further explore to a borderline result on primary analysis. Results: A higher genetically-predicted risk of endometriosis was not associated with risk of atrial fibrillation (OR 1.06, 95%CI 1.00 to 1.12, p=0.059), coronary artery disease (OR 1.00, 95%CI 0.93 to 1.07, p=0.933), heart failure (OR 1.00, 95%CI 0.94 to 1.05, p=0.920), or ischaemic stroke (OR 0.97, 95%CI 0.91 to 1.03, p=0.342). Replication analysis using a different data source for atrial fibrillation corroborated a lack of association (OR 1.02, 95%CI 0.96 to 1.09, p=0.488). There were no associations with any of measures of cardiac structure and function, as displayed in Figure 1. Conclusions: The results do not support a causal role of endometriosis in determining the risk of cardiovascular diseases, and in promoting an adverse cardiac structure and function.