Objective:Although numerous observational studies have revealed a correlation between leukocyte telomere length(LTL)and female reproductive system diseases(RSDs),the findings of these studies have tended to be consist...Objective:Although numerous observational studies have revealed a correlation between leukocyte telomere length(LTL)and female reproductive system diseases(RSDs),the findings of these studies have tended to be consistent.In this study,we accordingly sought to clarify the causal relationships between LTL and RSDs.Methods:We performed a bidirectional two-sample Mendelian randomization(MR)analysis using pooled statistics from genome-wide association studies of LTL and nine female RSDs.The final results were analyzed using five MR methods,with the inverse variance weighted(IVW)method used as the primary outcome.We applied MR-PRESSO to exclude outliers.Sensitivity analyses were also conducted to assess heterogeneity and pleiotropy.Results:In the forward MR analysis,a genetic prediction of longer LTLs was found to be causally associated with higher risks of endometriosis(IVW:odds ratio[OR]=1.25,95%confidence interval[CI]=1.06-1.46,P=0.008),leiomyoma of the uterus(IVW:OR=1.73,95%CI=1.52-1.98,P=4.9E-16),and ovarian cysts(IVW:OR=1.31,95%CI:1.19-1.45,P=1.5E-07).In the reverse MR results,female RSDs were shown to have no significant effect on LTLs(allP values>0.05).Sensitivity analysis confirmed the robustness of these results.Conclusions:Our findings substantiate the assumption that a genetically predicted longer LTL elevates the risk of endometriosis,leiomyoma of the uterus,and ovarian cysts,with no influence of RSDs on LTL.These findings contribute to establishing a causal link between LTL and RSDs,overcoming the constraints of earlier observational studies.They also imply that LTL could potentially serve as a biomarker for the occurrence of endometriosis,leiomyoma of the uterus,and ovarian cysts.展开更多
基金National Key Research and Development Program of China(2021YFC2700701,2022YFC2703803,2022YFC2703001)National Natural Science Foundation of China(82088102,82071731,82171613,8227034,81601238)+9 种基金Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2019-I2M-5-064)Science and Technology Commission of Shanghai Municipality(21Y11907600)Shanghai Municipal Commission of Health and Family Planning(20215Y0216)Collaborative Innovation Program of Shanghai Municipal Health Commission(2020CXJQ01)Clinical Research Plan of Shanghai Hospital Development Center(SHDC2020CR1008A)Shanghai Clinical Research Center for Gynecological Diseases(22MC1940200)Shanghai Urogenital System Diseases Research Center(2022ZZ01012)Shanghai Frontiers Science Research Base of Reproduction and Development,The Science and Technology Commission of Quzhou Municipality(2022K54)Open Fund Project of Key Laboratory of Reproductive Genetics,Ministry of Education,Zhejiang University(KY2022035)Open Fund Project of Guangdong Academy of Medical Sciences(YKY-KF202202)。
文摘Objective:Although numerous observational studies have revealed a correlation between leukocyte telomere length(LTL)and female reproductive system diseases(RSDs),the findings of these studies have tended to be consistent.In this study,we accordingly sought to clarify the causal relationships between LTL and RSDs.Methods:We performed a bidirectional two-sample Mendelian randomization(MR)analysis using pooled statistics from genome-wide association studies of LTL and nine female RSDs.The final results were analyzed using five MR methods,with the inverse variance weighted(IVW)method used as the primary outcome.We applied MR-PRESSO to exclude outliers.Sensitivity analyses were also conducted to assess heterogeneity and pleiotropy.Results:In the forward MR analysis,a genetic prediction of longer LTLs was found to be causally associated with higher risks of endometriosis(IVW:odds ratio[OR]=1.25,95%confidence interval[CI]=1.06-1.46,P=0.008),leiomyoma of the uterus(IVW:OR=1.73,95%CI=1.52-1.98,P=4.9E-16),and ovarian cysts(IVW:OR=1.31,95%CI:1.19-1.45,P=1.5E-07).In the reverse MR results,female RSDs were shown to have no significant effect on LTLs(allP values>0.05).Sensitivity analysis confirmed the robustness of these results.Conclusions:Our findings substantiate the assumption that a genetically predicted longer LTL elevates the risk of endometriosis,leiomyoma of the uterus,and ovarian cysts,with no influence of RSDs on LTL.These findings contribute to establishing a causal link between LTL and RSDs,overcoming the constraints of earlier observational studies.They also imply that LTL could potentially serve as a biomarker for the occurrence of endometriosis,leiomyoma of the uterus,and ovarian cysts.
