This study aimed to evaluate whether there is a causal relationship between autoimmune thyroid disorders (AITDs) and telomere length (TL) in the European population and whether there is reverse causality. In this study, Mendelian randomization (MR) and colocalization analysis were conducted to assess the potential causal relationship between AITDs and TL using summary statistics from large-scale genome-wide association studies, followed by analysis of the relationship between TL and thyroid stimulating hormone and free thyroxine (FT4) to help interpret the findings. The inverse variance weighted (IVW) method was used to estimate the causal estimates. The weighted median, MR‒Egger and leave-one-out methods were used as sensitivity analyses. The IVW method results showed a significant causal relationship between autoimmune hyperthyroidism and TL (β = −1.93 × 10⁻²; p = 4.54 × 10⁻⁵). There was no causal relationship between autoimmune hypothyroidism and TL (β = −3.99 × 10⁻³; p = 0.324). The results of the reverse MR analysis showed that genetically TL had a significant causal relationship on autoimmune hyperthyroidism (IVW: odds ratio (OR) = 0.49; p = 2.83 × 10⁻⁴) and autoimmune hypothyroidism (IVW: OR = 0.86; p = 7.46 × 10⁻³). Both horizontal pleiotropy and heterogeneity tests indicated the validity of our bidirectional MR study. Finally, colocalization analysis suggested that there were shared causal variants between autoimmune hyperthyroidism and TL, further highlighting the robustness of the results. In conclusion, autoimmune hyperthyroidism may accelerate telomere attrition, and telomere attrition is a causal factor for AITDs.

中文翻译：

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自身免疫性甲状腺疾病与端粒长度之间的因果关系：孟德尔随机化和共定位研究

本研究旨在评估欧洲人群中自身免疫性甲状腺疾病（AITD）与端粒长度（TL）之间是否存在因果关系以及是否存在反向因果关系。在本研究中，利用大规模全基因组关联研究的汇总统计数据，进行孟德尔随机化（MR）和共定位分析，以评估 AITD 与 TL 之间的潜在因果关系，然后分析 TL 与促甲状腺激素和 TL 之间的关系。游离甲状腺素 (FT4) 有助于解释结果。使用逆方差加权（IVW）方法来估计因果估计。使用加权中位数、MR-Egger 和留一法作为敏感性分析。 IVW方法结果显示自身免疫性甲亢与TL之间存在显着的因果关系（β  = -1.93 × 10 ^-2；p  = 4.54 × 10 ^-5）。自身免疫性甲状腺功能减退症与 TL 之间不存在因果关系（β  = -3.99 × 10 ^-3；p  = 0.324）。反向MR分析结果显示，遗传性TL与自身免疫性甲状腺功能亢进症（IVW：优势比（OR）= 0.49；p  = 2.83 × 10 ^-4）和自身免疫性甲状腺功能减退症（IVW：OR = 0.86；p  = 7.46×10 ^-3 )。水平多效性和异质性测试都表明了我们双向 MR 研究的有效性。最后，共定位分析表明自身免疫性甲状腺功能亢进症和 TL 之间存在共同的因果变异，进一步凸显了结果的稳健性。总之，自身免疫性甲状腺功能亢进症可能会加速端粒磨损，而端粒磨损是 AITD 的致病因素。