Association of sleep traits, physical activity and leisure sedentary behavior with women’s reproductive health: a two-sample Mendelian randomization analysis

Background: Living habits affect women's endocrine and fertility over time with aging and in certain circumstances, according to which we can promote women's reproductive health by adjusting living habits. Methods: We utilized two-sampleMendelian randomization (TSMR) analysis with summary datasets from genome-wide association study (GWAS) to investigate the causal relationship between sleep traits, leisure sedentary behavior, physical activity and women’s reproductive health-related traits. Exposure genetic instruments were used as variants significantly related to traits. The inverse-variance weighted (IVW) method was used as the main analysis approach, and we also performed MR-Egger and weighted median to supplement the sensitivity test. Then, the horizontal pleiotropy was detected by using MRE intercept and MR-PRESSO methods, and the heterogeneity was assessed using Cochran’s Q statistics by IVW and MR-Egger. Results: We found evidence that insomnia showed a significant inverse causal association with the endometriosis [OR (95% CI) IVW = 1.80 (1.16, 2.80), P = 0.009], and with the abnormal menstruation [OR (95% CI) IVW = 2.37 (1.34, 4.20), P = 0.003]. What else the sleep duration has the negative relation menopause age (beta IVW = −0.034, P = 0.001), the long sleep duration might be the protective factor of endometriosis [OR (95% CI) IVW = 0.07 (0.01, 0.72), P = 0.024], strenuous sports were also negatively correlated with the female infertility[OR (95% CI) IVW = 0.10 (0.02, 0.68), P = 0.019]. In sensitivity analysis, we observed no sign of horizontal pleiotropy or heterogeneity. Conclusion: Our finding suggested insomnia was an adverse factor of endometriosis and abnormal menstruation, long sleep duration was a protective factor with endometriosis. Therefore, adequate sleep and regular schedule might decrease the risk of endometriosis and abnormal menstruation to guarantee the women reproductive health.