Association of obstructive sleep apnea syndrome with polycystic ovary syndrome through bidirectional Mendelian randomization

Abstract

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BackgroundObservational studies have established a link between polycystic ovary syndrome (PCOS) and obstructive sleep apnea syndrome (OSAS), with obesity being a significant confounding factor that complicates the understanding of causality. This study seeks to clarify the causal relationship by utilizing bidirectional two-sample Mendelian randomization (MR) analysis.MethodsA bidirectional MR strategy was implemented to investigate the potential causal relationship between PCOS and OSAS. Instrumental variables (IVs) for PCOS were sourced from a dataset comprising 3,609 cases and 229,788 controls. For OSAS, statistical data were obtained from a genome-wide association study (GWAS) involving 38,998 subjects, alongside a control group of 336,659 individuals. Our MR analysis utilized several methods, including inverse variance weighted (IVW), weighted mode, weighted median, simple mode, and MR-Egger, primarily focusing on the IVW technique. Sensitivity tests were conducted to ensure the robustness of our findings.ResultsUtilizing the IVW method, we identified a notable causal association from OSAS to PCOS, with an odds ratio (OR) of 1.463 and a 95% confidence interval (CI) of 1.086–1.971 (p = 0.012). In the opposite direction, PCOS also appeared to significantly affect OSAS development, indicated by an OR of 1.041 and a 95% CI of 1.012–1.072 (p = 0.006). The MR-Egger intercept test showed no evidence of directional pleiotropy, affirming the credibility of our causal findings (p > 0.05).ConclusionThis study suggests a bidirectional causal relationship between PCOS and an increased risk of OSAS. These insights could guide future screening and prevention strategies for both conditions.

Keywords

• PCOS
• OSAS
• Mendelian randomization
• causal inference
• GWAS