Deciphering the Bidirectional Impact of Leukocyte Telomere Length on Multiple Sclerosis Progression: A Mendelian Randomization Study Publisher Pubmed



Sabaie H¹ ; Taghavi Rad A² ; Shabestari M³ ; Seddiq S⁴ ; Saadattalab T⁵ ; Habibi D⁶ ; Saeidian AH⁷ ; Abbasi M⁸ ; Mirtavoosmahyari H⁹
Source: Multiple Sclerosis and Related Disorders Published:2025

Abstract

Observational studies have suggested a link between leukocyte telomere length (LTL) and multiple sclerosis (MS) progression, but the causal relationship remains uncertain. This study investigates the causal association between LTL and MS progression using a bidirectional two-sample Mendelian randomization (MR) approach. We analyzed genome-wide association summary statistics data from 472,174 individuals for LTL and 12,584 MS patients for disease progression. The primary method was the inverse variance weighted (IVW) approach, supported by sensitivity analyses to ensure robustness. The forward analysis revealed a significant positive causal relationship between LTL and MS progression (β = 0.107, 95 % CI = 0.006 to 0.209, P = 0.037). Conversely, the reverse analysis indicated a negative causal relationship (β = -0.010, 95 % CI = -0.020 to -0.001, P = 0.037). No heterogeneity or horizontal pleiotropy was found, and the sensitivity analyses confirmed consistent results. These findings suggest that telomere dynamics play a complex role in MS progression and highlight their potential as therapeutic targets. Further research is essential to uncover the biological mechanisms underlying the influence of telomeres on MS progression. © 2025