Bidirectional Mendelian randomization reveals associations between telomere length and autoimmune diseases

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.

Our bidirectional Mendelian randomization analysis was aimed to evaluate the causal association between autoimmune diseases and telomere length.

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.

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).

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.