Sabaie Hani, Taghavi Rad Ali, Shabestari Motahareh, Seddiq Sahar, Saadattalab Toktam, Habibi Danial, Saeidian Amir Hesam, Abbasi Mohadeseh, Mirtavoos-Mahyari Hanifeh
Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
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.
Mult Scler Relat Disord. 2025 Feb;94:106277. doi: 10.1016/j.msard.2025.106277. Epub 2025 Jan 16.
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.
观察性研究表明白细胞端粒长度（LTL）与多发性硬化症（MS）进展之间存在联系，但因果关系仍不确定。本研究采用双向双样本孟德尔随机化（MR）方法，调查LTL与MS进展之间的因果关联。我们分析了来自472174名个体的全基因组关联汇总统计数据以获取LTL，并分析了12584名MS患者的疾病进展数据。主要方法是逆方差加权（IVW）方法，并通过敏感性分析来确保稳健性。正向分析显示LTL与MS进展之间存在显著的正因果关系（β = 0.107，95%CI = 0.006至0.209，P = 0.037）。相反，反向分析表明存在负因果关系（β = -0.010，95%CI = -0.020至-0.001，P = 0.037）。未发现异质性或水平多效性，敏感性分析证实了一致的结果。这些发现表明端粒动态在MS进展中起复杂作用，并突出了它们作为治疗靶点的潜力。进一步的研究对于揭示端粒影响MS进展的生物学机制至关重要。
