Sleep traits and risk of premature ovarian insufficiency - two-sample and multivariate mendelian randomisation analysis.

Introduction: Premature ovarian insufficiency (POI), a cause of hormonal imbalance and infertility, may be linked to sleep patterns, but the exact relationship is unclear. This study uses Mendelian randomisation (MR) to investigate the causal link between sleep traits and POI, aiming to uncover new treatment methods. Material and methods: Data from genome-wide association studies were used to examine 11 sleep traits related to POI. The primary method for assessing causality was the inverse variance weighted (IVW) approach, with MR-Egger regression as a secondary analysis. Sensitivity analyses included Cochrane's Q statistic, the MR-Egger intercept test, leave-one-out cross-validation, and funnel plot inspections. A multivariate MR analysis combined significant exposure factors from 2 independent samples to determine their cumulative impact on POI incidence. Results: The two-sample MR analysis using the IVW method showed a positive causal link between sleep duration and POI (p = 0.037). A negative causal link was found between sleep chronotype and POI (p = 0.032). Cochrane's Q test showed no significant heterogeneity, and MR-Egger intercept analysis indicated no directional pleiotropy. Leave-one-out analysis confirmed the robustness of the findings, and funnel plots showed symmetrical distribution, suggesting no bias. Multivariate MR analysis found no combined causal effect of sleep duration and chronotype on POI risk. Conclusions: Our study suggests a causal link between sleep traits and POI through Mendelian randomisation. Enhancing sleep habits could reduce POI risk, highlighting sleep hygiene's role in women's reproductive health and opening avenues for new prevention and treatment methods.