Telomere length and the risk of infertility: A Mendelian randomization study

Abstract

Abstract Purpose As people age, fertility tends to decline, and various previous studies have indicated a potential connection between aging and infertility. However, whether telomere length (TL), as a marker of cellular age, is causally related to infertility remains an unknown question. Methods In this research, we performed two-sample Mendelian randomization (MR) study to evaluate the causal relationship between TL and infertility risk. We mainly conducted MR analyses employing the inverse variance weighted (IVW) method and complemented with other MR methods. Additionally, sensitivity analysis was performed to testify the primary results' robustness. Results The summary dataset of the genome-wide association studies (GWAS) for TL (n = 472,174) were obtained from the UK Biobank. Four infertility subgroups based on gender and etiology were selected from FinnGen Consortium R6 release, which included 119,206 (Female infertility_1), 118,644 (Female infertility_2) ,128,432 (Female infertility_3) and 74,159 (Male infertility) individuals, respectively. 137 single-nucleotide polymorphisms (SNPs) associated with TL in European populations were selected as instrumental variables (IVs). We found that genetically determined TL and epigenetic clocks were not individually associated with 4 types infertility(IVW p > 0.05), and this result was consistent across sensitivity analyses. Our findings indicate that there was no causal association between genetically determined TL and epigenetic clocks with the four types of infertility (IVW p > 0.05). Other methods also achieved consistent results. Sensitivity analyses were performed and revealed no heterogeneity and horizontal pleiotropy. Conclusions Our findings suggest that TL may not serve as effective causal biomarkers for predicting infertility and need more robust analytical methods and more comprehensive researches.