Causal Evidence of the Relationship Between Polycystic Ovary Syndrome and Obstructive Sleep Apnea in European and East Asian Populations: a Two-sample Mendelian Randomization Study

Background: Several studies have documented the high prevalence of obstructive sleep apnea (OSA) among women with polycystic ovary syndrome (PCOS). However, causal relationships between the two conditions remain unconfirmed. This study aims to assess the causal relationships between OSA and PCOS.

Methods: We conducted a two-sample Mendelian randomization (MR) analysis utilizing instrumental variables (IVs) derived from large-scale genome-wide association studies (GWAS) to genetically estimate the causal effects of PCOS on OSA. To explore the impact of PCOS on OSA across different ethnicities, we analyzed GWAS data from European and East Asian participants. The inverse variance weighted (IVW) method was the primary statistical approach. A series of sensitivity analyses, including the weighted median, MR-Egger, weighted mode methods, and leave-one-out analysis, were performed to evaluate the robustness of our MR results.

Results: In the IVW analysis, the odds ratio (OR) for the association between PCOS and OSA was 1.133 [95% confidence interval (CI): 1.037-1.239, P=0.006], indicating that PCOS significantly increases the risk of OSA in the European population. No evidence of heterogeneity or directional pleiotropy was found using Cochran's Q test and the MR-Egger test. Conversely, the IVW analysis did not reveal a causal effect of PCOS on OSA in the East Asian population (OR =1.061, 95% CI: 0.888-1.268, P=0.51).

Conclusions: Our findings suggest that European women with PCOS are at an increased risk for OSA. However, no association was observed between PCOS and OSA in the East Asian population. Clinicians should maintain a high index of suspicion for OSA in women with PCOS, particularly among the European demographic.