Bidirectional Mendelian randomization reveals associations between telomere length and autoimmune diseases

被引：0
作者：
Qin Jiang [1 ]
Chenxi Yu [2 ]
Shiben Zhu [3 ]
Yang Liu [1 ]
Min Ye [2 ]
机构：
[1] School of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Hubei, Wuhan
[2] Department of Spleen and Gastroenterology, Hubei Provincial Hospital of Traditional Chinese Medicine, Affiliated Hospital of Hubei University of Chinese Medicine, Hubei, Wuhan
[3] Hubei Shizhen Laboratory, Hubei, Wuhan
[4] Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou
[5] Department of General Affairs, Shenzhen Baoan Women’s and Children’s Hospital, Guangdong, Shenzhen
来源：
Trials | / 26卷 / 1期
关键词：
Autoimmune diseases; Casual effect; Graves; disease; GWAS; Mendelian randomization; Psoriasis; Rheumatoid arthritis; Systemic lupus erythematosus; Telomere length; Type; 1; diabetes;
D O I：
10.1186/s13063-025-08831-9
中图分类号：
学科分类号：
摘要：
Background : Autoimmune diseases are a group of complex chronic illnesses that affect multiple organs or body systems. These diseases are characterized by tissue damage, impaired organ function, and increased risk of malignancies, and elevated mortality. Nevertheless, the casual correlation between autoimmune diseases and telomere length remains uncertain. Objective: Our bidirectional Mendelian randomization analysis was aimed to evaluate the causal association between autoimmune diseases and telomere length. Methods: To minimize bias, four demographic factors including body mass index (BMI), alcohol consumption, smoking, and income were assessed using two-sample Mendelian randomization analysis. Furthermore, this analysis was conducted to explore the causal relationships between telomere length and autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes (T1D), Graves’ disease (GD), and psoriasis using two separate datasets from FinnGen and the UK Biobank. Results: When using inverse variance weighting (IVW) to assess the relationship between four available demographic factors and overall autoimmune diseases, no significant association was found (p > 0.05). However, a significant negative causal effect of telomere length on autoimmune diseases was observed (IVW: OR = 0.906, 95% CI = 0.832–0.986, p = 0.022). Reverse Mendelian randomization analysis revealed no significant correlation. Further analysis using two separate datasets for five common autoimmune diseases confirmed significant negative associations between telomere length and RA (UKB biobank: OR = 0.997, 95% CI 0.994–0.999, p = 0.025; FinnGen: OR = 0.860, 95% CI 0.741–0.998, p = 0.047), GD (UK Biobank: OR = 0.519, 95% CI 0.430–0.625, p < 0.001; FinnGen: OR = 0.623, 95% CI 0.496–0.785, p < 0.001), and psoriasis (UK Biobank: OR = 0.772, 95%CI = 0.642–0.928, p = 0.006; FinnGen: OR = 0.841, 95%CI = 0.727–0.973, p = 0.020). A significant positive association was found for SLE in the UK Biobank (OR = 1.718, 95% CI = 95% CI 1.155–2.558, p = 0.007). Reverse Mendelian randomization analysis identified a significant negative association between telomere length and SLE (UK Biobank: OR = 0.995, 95% CI 0.991–0.998, p = 0.014; FinnGen: OR = 0.988, 95% CI 0.977–0.998, p = 0.029) and psoriasis (FinnGen: OR = 0.992, 95% CI 0.988–0.997, P = 0.005), and a positive association with RA (UK Biobank: OR = 1.988 95% CI 1.056–3.743, p = 0.031). Conclusions: This Mendelian randomization analysis reveals a significant association between telomere length and autoimmune diseases such as RA, GD, and psoriasis, while a positive relationship was validated with SLE. These findings underscore the need for further investigation to better understand the underlying mechanisms and their potential clinical applications. © The Author(s) 2025.
引用
收藏
相关论文
共 37 条
  • [1] Rose N.R., Prediction and prevention of autoimmune disease in the 21st century: a review and preview, Am J Epidemiol, 183, 5, pp. 403-406, (2016)
  • [2] Conrad N., Misra S., Verbakel J.Y., Et al., Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK, Lancet, 401, pp. 1878-1890, (2023)
  • [3] Xu Q., Ni J.J., Han B.X., Et al., Causal relationship between gut microbiota and autoimmune diseases: a two-sample Mendelian randomization study, Front Immunol, 12, (2021)
  • [4] Ward M.M., Chapter 19 - Epidemiology of SLE and related diseases: Incidence, prevalence, and mortality, Lahita’s Systemic Lupus Erythematosus (Sixth Edition), pp. 291-304, (2021)
  • [5] Wu L., Lin H., Hu Y., Et al., The major causes and risk factors of total and cause-specific mortality during 5.4-year follow-up: the Shanghai Changfeng study, Eur J Epidemiol, 34, 10, pp. 939-949, (2019)
  • [6] Kurosaka D., Yasuda J., Yoshida K., Et al., Telomerase activity and telomere length of peripheral blood mononuclear cells in SLE patients, Lupus, 12, 8, pp. 591-599, (2003)
  • [7] Steer S.E., Williams F.M.K., Kato B., Et al., Reduced telomere length in rheumatoid arthritis is independent of disease activity and duration, Ann Rheum Dis, 66, 4, pp. 476-480, (2007)
  • [8] Artlett C.M., Black C.M., Briggs D.C., Stevens C.O., Welsh K.I., Telomere reduction in scleroderma patients: a possible cause for chromosomal instability, Br J Rheumatol, 35, 8, pp. 732-737, (1996)
  • [9] Jeanclos E., Krolewski A., Skurnick J., Et al., Shortened telomere length in white blood cells of patients with IDDM, Diabetes, 47, 3, pp. 482-486, (1998)
  • [10] Davey Smith G., Hemani G., Mendelian randomization: genetic anchors for causal inference in epidemiological studies, Hum Mol Genet, 23, R1, pp. R89-R98, (2014)
1234