Causal relationships between leukocyte telomere length and female reproductive system diseases: a bidirectional Mendelian randomization study.

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 [] = 1.25, 95% confidence interval [] = 1.06-1.46,  = 0.008), leiomyoma of the uterus (IVW:  = 1.73, 95% = 1.52-1.98,  = 4.9E-16), and ovarian cysts (IVW:  = 1.31, 95% :1.19-1.45,  = 1.5E-07). In the reverse MR results, female RSDs were shown to have no significant effect on LTLs (all 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.