Bidirectional Mendelian Randomization Analysis of the Association between Telomere Length and the Risk of Vascular Dementia and Idiopathic Normal Pressure Hydrocephalus

Abstract

Background: Idiopathic normal pressure hydrocephalus (INPH) and vascular dementia (VaD) are uncommon age-related conditions. Previous research indicated that telomere shortening is associated with aging and the emergence of age-related ailments. However, the correlation between genetically predicted telomere length (TL) and the susceptibility to INPH and VaD remains uncertain. This study seeks to examine the underlying causality of TL with the risk of INPH and VaD by employing Mendelian randomization (MR) analysis. Methods: A bidirectional MR was conducted to evaluate the potential causality of TL with the risk of INPH and VaD. Five MR methods were employed for result analysis, with the inverse variance weighted (IVW) method as the main technique. Additionally, various sensitivity analyses were performed to assess the presence of heterogeneity and pleiotropy in the study findings. Results: In the forward MR analysis, both the IVW analyses suggested an underlying causality, indicating that longer TL may correlate with a reduced incidence of INPH (IVW: OR = 0.44, 95% CI: 0.25–0.77, p = 0.004) and VaD (IVW: OR = 0.31, 95% CI: 0.12–0.82, p = 0.018). No heterogeneity or horizontal pleiotropy was observed. However, reverse MR analysis failed to uncover an underlying causality between INPH, VaD, and TL. Conclusion: There could be a potential correlation of longer TL with the decreased risk of INPH and VaD within the European population. This research offers fresh perspectives on the association of TL with the risk of INPH and VaD.