No genetic causal association between polycystic ovary syndrome and the risk of cardiovascular diseases: A mendelian randomization study

Abstract Objective Polycystic ovary syndrome (PCOS) is one of the risk factors for cardiovascular diseases (CVDs). However, the possible association between PCOS and common CVDs remains inconclusive. The aim of this study was to explore the potential relationship between PCOS and CVDs. Methods We conducted two-sample Mendelian randomization (MR) analyses. In our study, 14 single nucleotide polymorphisms (SNPs) in Europeans and another 13 SNPs in Asians were applied as instrumental variables for PCOS. The largest published meta-genome-wide association studies of European ancestry and the BioBank Japan Project of Asian ancestry were used to collect the outcome data. MR analysis was performed using inverse variance weighting as the primary method. Several sensitivity analyses and instrumental variable strength evaluations were also performed to verify the reliability of results. Results Our analysis revealed that any potential causal association between genetically-predicted PCOS and the risk of CVDs do not exist. These CVDs include peripheral artery disease, atrial fibrillation, arrhythmia, cardiovascular diseases, heart failure, peripheral vascular disease, hypertension, ischemic stroke, myocardial infarction and venous thromboembolisms. Associations could not be found even after the SNPs linked to these possible confounders (body mass index, waist-to-hip ratio, and serum testosterone) were deleted. Sensitivity analysis demonstrated no presence of horizontal pleiotropy or heterogeneity. Conclusion The present mendelian randomization study suggests that genetically-predicted PCOS may not be associated with the risk of CVDs.