Causal Relationships Among Lifestyle, Lipidome, and Polycystic Ovary Syndrome: A Mendelian Randomization Study.

BACKGROUND

Lifestyle interventions often influence lipid levels in patients with polycystic ovary syndrome (PCOS), thereby modulating disease progression. However, whether lipid levels play a mediating role remains unclear.

OBJECTIVE

To investigate causal associations between lifestyle, lipidome, and PCOS, as well as mediating role of lipidome.

METHODS

This study employed a bidirectional two-sample Mendelian randomization (MR) analysis, with lifestyle and lipidome as exposures and PCOS as outcome. A two-step MR approach was used to assess mediating role of lipidome. Inverse-variance weighted (IVW) method was primarily applied, and sensitivity analyses were conducted to test robustness of results.

RESULTS

Overall physical activity time (OR = 0.590, 95% CI: 0.394-0.882, P = 0.010) was significantly negatively associated with PCOS risk, while leisure screen time (OR = 1.377, 95% CI: 1.050-1.804, P = 0.021) was significantly positively associated with PCOS risk. 25 lipid levels were significantly associated with PCOS risk, with 3 showing negative correlations and 22 showing positive correlations (P < 0.05). Mediation analysis revealed that TAG (50:1) (triacylglycerol with 50 carbon atoms and 1 double bond) levels mediated causal relationship between increased overall physical activity time and lowered PCOS risk. The median effect accounted for 23.8% of the total effect (B = -0.126, 95% CI: -0.238 to -0.014, P = 0.027).

CONCLUSION

This study revealed causal associations between overall physical activity time, leisure screen time, and PCOS, and identified mediating role of TAG (50:1) levels. These findings provide scientific insights for lifestyle management in PCOS patients.