Abstract
Evidence have indicated a correlation between sleep disorders and endometriosis, but the causal relationship remains uncertain. This study utilized Mendelian randomization (MR) approach to investigate the causal associations between sleep disorders and endometriosis. We conducted bidirectional 2-sample MR using inverse variance weighting as the primary analysis to assess forward and reverse causality. Multivariable Mendelian randomization were also utilized to adjust for confounders, reducing pleiotropy and residual confounding. Univariable MR analysis demonstrated a positive causal effect of insomnia on endometriosis (inverse variance weighting odds ratio: 2.021, 95% confidence interval: 1.280-3.192, P = .003). Multivariable Mendelian randomization analysis further confirmed that the robustness of the causal association between insomnia and endometriosis after adjusting for key confounders, such as body mass index, alcohol intake, smoking, and depression. However, no causal associations were detected between endometriosis and other sleep-related traits, including chronotype, sleep duration, daytime napping, and daytime sleepiness. This MR study gave novel genetic evidence supporting insomnia as an independent risk factor for endometriosis. These findings highlight the need for greater attention to endometriosis-related sleep disorders in both clinical practice and medical research.