Mendelian randomization study shows no causal effects of polycystic ovarian syndrome on the risk of preeclampsia

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Abstract Background Previous studies have shown an association between polycystic ovary syndrome (PCOS) and the increased risk of developing preeclampsia (PE). However, other studies have not found an independent association between the two. A causal association between PCOS and PE remains unclear. The objective of this study was to determine whether PCOS has a causal relationship with PE. Methods A two-sample Mendelian randomization (MR) analysis was performed by using the inverse‐variance weighted (IVW), weighted median, MR‐Egger regression, simple mode, and weighted mode methods. We used the publicly available summary statistics data sets of genome‐wide association studies (GWAS) meta‐analyses for PCOS (N = 113238) as the exposure and a GWAS for PE (N = 267242) as the outcome. In addition, the heterogeneity, horizontal pleiotropy, and stability were assessed through several sensitivity analyses. Results 13 single nucleotide polymorphisms (SNPs) at genome-wide significance from GWASs on PCOS were selected as the instrumental variables (IVs). The results of all the methods including IVW, weighted median, MR‐Egger regression, simple mode, and weighted mode were consistent and showed no causal association between PCOS and PE (P > 0.05) Conclusion The results of MR analysis support that PCOS may not be causally associated with an increased risk of PE. We suggest PCOS should not be presently included as a risk factor in obstetrical guidelines and prediction models for PE. To determine whether PCOS and PE are associated, further research is needed.

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