Genetically Predicted Causal Relationship Between Polycystic Ovary Syndrome and Preeclampsia

Clarifying the causal relationship between polycystic ovary syndrome (PCOS) and its characteristic markers with preeclampsia (PE) is of utmost importance in preventing the development of PE. Observational studies have investigated the relationship, but the conclusions have been inconsistent.

Utilizing publicly accessible genomewide association study (GWAS) data, we performed a two-sample Mendelian randomization analysis to investigate causal relationships between PCOS, its characteristic biomarkers, and PE. The inverse variance weighting (IVW) method served as the primary analytical approach. To ensure methodological rigor, we assessed potential pleiotropy using the MR-Egger intercept and evaluated heterogeneity through Cochran's Q test with associated p values.

The study's results showed a causal relationship between PCOS and PE (IVW OR = 1.172, 95% CI: 1.003-1.371, p = 0.046). Using the IVW method, we also discovered that characteristic indicators of PCOS, including decreased high-density lipoprotein (HDL) levels, increased body mass index (BMI), and elevated fasting insulin levels, pose a risk for PE. At the same time, there is no clear causal relationship between low-density lipoprotein (LDL), total cholesterol (TC), triglycerides (TGs), testosterone (T), fasting blood glucose (FBG), and circulating sex hormone-binding globulin (SHBG) and PE.

Our research results provide new evidence at the genetic prediction level for PCOS as a risk factor for PE. Furthermore, analysis of PCOS characteristics suggests that HDL levels, BMI, and fasting insulin levels may be causally associated with PE. These findings provide a novel theoretical basis and practical strategies for the clinical management of women with PCOS, aimed at predicting and preventing PE.