A Mendelian Randomization Study of the Association Between Polycystic Ovary Syndrome and Serum Urea Levels

Polycystic Ovary Syndrome (PCOS) is a common endocrine and metabolic disorder affecting the reproductive function of women of reproductive age. Its clinical features include irregular menstruation, obesity, insulin resistance, hyperandrogenism, and polycystic ovarian morphology. Elevated serum urea levels may be related to the pathogenesis of PCOS. However, existing observational studies have not been able to clarify the causal relationship between serum urea levels and PCOS.

This study employed a two-sample Mendelian randomization (MR) approach to evaluate the genetic causal relationship between serum urea levels and PCOS. We utilized summary data from genome-wide association studies (GWAS) from the UK Biobank for serum urea levels as the exposure variable, and from the FinnGen consortium for PCOS. Causal association analyses were conducted using inverse-variance weighting (IVW), MR Egger, weighted median, and simple mode methods. Additionally, Cochrane's Q test was applied to assess heterogeneity in the MR results, and potential horizontal pleiotropy was evaluated using the MR-Egger intercept test and the MR-PRESSO method.

IVW analysis revealed a statistically significant causal relationship between serum urea levels and PCOS(OR = 1.623,95% CI=1.015-2.597,P=0.043). Further analysis found no significant evidence of horizontal pleiotropy (P=0.674),and leave-one-out analysis confirmed the robustness of the causal association.

In this two-sample MR analysis, we present the evidence of a genetic causal relationship between serum urea levels and PCOS, thereby offering a novel perspective on the pathogenesis of this disease.