Leukocyte telomere length is associated with increased risk of endometriosis: a bidirectional two-sample Mendelian randomization study

Abstract

BackgroundEndometriosis (EMs) is a common gynecological disorder. Observational studies on the relationship between leukocyte telomere length (LTL) and EMs have shown conflicting results. The purpose of this study was to evaluate the precise causal relationship between LTL and EMs using Mendelian randomization (MR) methodology.MethodsWe employed MR to assess the causal relationship between LTL and EMs. Summary data from several large-scale genome-wide association studies (GWAS) were used for bidirectional two-sample MR analysis. Sensitivity analyses were conducted to ensure the robustness of our results. All analyses were also replicated in another completely independent EMs dataset.ResultsOur MR analysis indicated that genetically predicted longer LTL increased the risk of EMs (IVW: discovery, OR=1.169, 95%CI: 1.059-1.290, p=0.002; validation, OR=1.302, 95%CI: 1.140-1.487, p=0.000), while EMs had no causal impact on LTL (IVW: discovery, OR=1.013, 95%CI: 1.000-1.027, p=0.056; IVW: validation, OR=1.005, 95%CI: 0.995-1.015, p=0.363). Causal estimates were supported by various calculation models (including MR-Egger, Weighted median, MR-PRESSO, and MR-RAPS). Heterogeneity and pleiotropy analyses also indicated robustness of the results.ConclusionOur findings substantiate the idea that a genetically predicted longer LTL elevates the risk of EMs, with no influence of EMs on LTL risk. This research bolsters the causal link between LTL and EMs, overcoming the constraints of earlier observational studies. It implies that LTL may potentially function as a biomarker for EMs, opening up novel possibilities for EMs prevention and treatment.

Peripheral blood leukocyte Telomere length and endometriosis: A Mendelian randomization study

“…In our research, we addressed these limitations by using MR to probe the causal association between LTL and the incidence of endometriosis. Our study suggests that LTL is a danger element for endometriosis, aligning with previous reports by Bai et al [ 20 ]. However, our subtype analysis revealed that longer LTL specifically increases the risk for only three endometriosis subtypes.…”

Casual effects of telomere length on sarcoidosis: a bidirectional Mendelian randomization analysis

“…To gauge the IVs strength, we computed the -statistic for each SNP as well as for the entire set of SNPs. The -statistic for a single SNP was calculated using the following formula ( 39 ) , with “ ” representing the impact of the IV on the exposure, and “ ” indicating the standard error of “ .” Meanwhile, the total -statistic followed this formula: , where “ ” stands for the sample size for the exposure, “ ” represents the number of SNPs. The variable “ ” depicts the fraction of exposure variance elucidated by SNPs and is calculated using the formula , where “ ” represents the effect allele frequency of the SNP, and “ ” signifies the SNP’s influence on the exposure.…”

Casual Effects of Telomere Length on Sarcoidosis: A Bidirectional Mendelian Randomisation Analysis

“…To gauge the IVs strength, we computed the -statistic for each SNP as well as for the entire set of SNPs. The -statistic for a single SNP was calculated using the following formula 27 , with " " representing the impact of the IV on the exposure, and " " indicating the standard error of " ". Meanwhile, the total -statistic followed this formula: , where " " stands for the sample size for the exposure, " " represents the number of SNPs.…”