The causal relationship between autoimmune thyroid disorders and telomere length: A Mendelian randomization and...

Area of Science:

• Genetics
• Endocrinology
• Immunology

Background:

• Autoimmune thyroid disorders (AITDs) are common endocrine conditions.
• Telomere length (TL) is associated with aging and cellular senescence.
• The causal relationship between AITDs and TL remains unclear.

Purpose of the Study:

• To investigate the potential causal relationship between AITDs and TL in a European population.
• To assess for reverse causality, where TL might influence AITDs.
• To explore the genetic underpinnings of the association between TL and thyroid function.

Main Methods:

• Bidirectional Mendelian randomization (MR) analysis using summary statistics from large-scale genome-wide association studies.
• Inverse variance weighted (IVW) method for causal estimates.
• Sensitivity analyses including weighted median, MR-Egger, and leave-one-out methods.
• Colocalization analysis to identify shared causal variants.

Main Results:

• A significant causal relationship was found between autoimmune hyperthyroidism and shorter TL (β = -1.93 × 10⁻², p = 4.54 × 10⁻⁵).
• No significant causal relationship was observed between autoimmune hypothyroidism and TL (β = -3.99 × 10⁻³, p = 0.324).
• Reverse MR analysis indicated that genetically determined TL influences both autoimmune hyperthyroidism (OR = 0.49, p = 2.83 × 10⁻⁴) and autoimmune hypothyroidism (OR = 0.86, p = 7.46 × 10⁻³).
• Colocalization analysis supported shared causal variants between autoimmune hyperthyroidism and TL.

Conclusions:

• Autoimmune hyperthyroidism may accelerate telomere attrition.
• Telomere attrition appears to be a causal factor for AITDs.
• These findings highlight a complex bidirectional relationship between TL and AITDs, particularly autoimmune hyperthyroidism.