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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
Authors
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Authors Affiliations
  1. 1. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
  2. 2. Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  3. 3. Yazd Cardiovascular Research Center, Non-Communicable Diseases Research Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
  4. 4. Osteoporosis Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Epidemiology and Biostatistics, School of Public Health, Babol University of Medical Sciences, Babol, Iran
  7. 7. Department of Surgery, Rasool-E Akram Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
  8. 8. Department of Biology and Biochemistry, University of Houston (UH)
  9. 9. Lung Transplantation Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

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
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