The genetic association between polycystic ovary syndrome and the risk of hypertensive disorders of pregnancy: A Mendelian randomization study

Objective: In observational studies, polycystic ovary syndrome (PCOS) has been associated with an increased risk of hypertensive disorders of pregnancy (HDPs); however, the causality between these conditions remains to be determined. This study aimed to investigate the causal relationship between PCOS and HDPs.

Methods: This genome-wide association study (GWAS), conducted from November to December 2023, aimed to investigate the causal relationships between PCOS and HDPs, gestational hypertension and preeclampsia/eclampsia via two-sample Mendelian randomization (MR) analysis. European-lineage GWAS summary statistics were obtained from a PCOS GWAS meta-analysis, the FinnGen consortium and the UK Biobank. The primary method employed was inverse-variance weighted MR, with several sensitivity analyses and evaluations of instrumental variable strength conducted to ensure result reliability.

Results: The odds ratios (ORs) for the effects of PCOS on the risk of HDPs, gestational hypertension and preeclampsia/eclampsia were 1.007 (95 % confidence interval [CI]: 0.888-1.142; P = 0.911), 1.024 (95 % CI: 0.901-1.163; P = 0.719) and 0.992 (95 % CI: 0.828-1.187; P = 0.926), respectively. These results were found to be robust following confirmation via the Q test, MR-Egger intercept analysis, and MR-PRESSO analysis. Furthermore, a sensitivity analysis excluding the single nucleotide polymorphisms associated with body mass index (BMI) also supported the convincing nature of the findings.

Conclusions: Our findings do not offer conclusive evidence of the impact of PCOS on HDPs. In light of these results, efforts to prevent HDPs in women with PCOS should focus on women with high-risk features rather than all women with PCOS.