Causal inference study on the influence of the anxious/worrier trait on the risk of endometriosis: Two-sample Mendelian randomization

Ruixue Wan, Fan W, Wen Fan, Dan Chen, Chen D, Wen Y, Ya Wen
International Journal of Gynecology & Obstetrics · 2026 · doi:10.1002/ijgo.71413 · PMID:42969190 · W7225120531
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Two-sample Mendelian randomization demonstrates that the anxious/worrier trait causally increases endometriosis risk, whereas endometriosis does not significantly affect emotional indicators.

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Abstract

OBJECTIVE: Recent observational studies have identified an association between the anxious/worrier trait and endometriosis. However, the causal nature of this relationship remains unclear. METHODS: Summary statistics from genome-wide association studies were used to identify independent genetic variants associated with the anxious/worrier trait, which served as instrumental variables in a two-sample Mendelian randomization (MR) study. Causal estimates for the effect of emotional factors on endometriosis risk were obtained using inverse variance weighting, MR-Egger regression, and weighted median methods. Reverse MR analysis was then used to assess the impact of endometriosis on emotional indicators. Sensitivity analyses included the MR-Egger intercept test, leave-one-out analysis, and Cochran's Q test, which were used to detect potential pleiotropy and heterogeneity. RESULTS: The inverse variance weighted analysis indicated that the anxious/worrier trait significantly elevated the risk of developing endometriosis (odds ratio 3.84; 95% confidence interval 1.42-10.41, P = 0.008). The results of the reverse MR analysis did not indicate a significant causal effect of endometriosis on emotional indicators (P > 0.05). CONCLUSION: This study provides genetic evidence for a causal relationship between emotional factors (anxious/worrier trait) and endometriosis. However, the specific biological pathways involved warrant further investigation.

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