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

Abstract

Background: Observational 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.

Methods: A 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.

Results: Utilizing 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).

Conclusion: This 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: GWAS; Mendelian randomization; OSAS; PCOS; causal inference.

Figure 1

Schematic illustration showing the two-way Mendelian Randomization method employed to investigate the causal connection between PCOS and OSAS. PCOS, Polycystic ovary syndrome; OSAS, Obstructive sleep apnea syndrome.

Figure 2

Depicts MR studies on the causal link with OSAS as the predictor and PCOS as the result. (A) Shows the causative influence of OSAS on PCOS. (B) A scatter diagram showing the analysis of individual SNPs to assess OSAS effect on the likelihood of PCOS. (C) A graph excluding one genetic variant shows the combined impact of SNPs on the link connecting OSAS with PCOS.

Figure 3

MR evaluations reveal causal relationships, with PCOS predicting OSAS the consequence. (A) Details the causative effect of PCOS on OSAS. (B) A scatter diagram examines the SNPs to understand how PCOS affects the onset OSAS. (C) A leave one out graph underscores the collective effects of SNPs and their impact link connecting PCOS and OSAS.