Causal association of metabolites and polycystic ovarian syndrome: A Mendelian randomization study

Abstract

Objective Polycystic ovarian syndrome (PCOS) is a common reproductive disorder that affects a considerable number of women worldwide. However, previous studies investigating the connection between metabolites and PCOS have produced conflicting results. The aim of this study was to explore the potential relationship between PCOS and metabolites using genetic polymorphisms. Methods We utilized a comprehensive two-sample Mendelian randomization (MR) analysis to examine the causal link between 1352 metabolites and PCOS. We employed complementary MR methods, such as the inverse-variance weighted (IVW) method, and conducted sensitivity analyses to evaluate the reliability of the outcomes. Reverse MR analysis was performed to evaluate the possibility of reverse causation. Results Five metabolites were identified to be significantly associated with PCOS risk: Methionine sulfoxide levels (IVW: OR [95%]: 1.549[1.274 to 1.883], p = 1.154E-5), Theophylline levels (IVW: OR [95%]: 0.725[0.589 to 0.890], p = 0.002), 4-hydroxycoumarin levels (IVW: OR [95%]: 0.786[0.658 to 0.940], p = 0.008), Tyramine O-sulfate levels (IVW: OR [95%]: 0.699[0.568 to 0.862], p = 0.0008), and Sulfate of piperine metabolite C16H19NO3 (3) levels (IVW: OR [95%]: 1.296[1.064 to 1.579], p = 0.009). We found PCOS was suggestively associated with decreased Tyramine O-sulfate levels using IVW method (OR [95%]: 0.953[0.917 to 0.991], p = 0.015) in the reverse MR analysis. The results of the sensitivity analyses were consistent with the main findings. Conclusion Our MR analysis provides strong evidence supporting a causal association between metabolites and the susceptibility of PCOS.