Division of Thyroid Surgery, Department of General Surgery, Laboratory of Thyroid and Parathyroid Diseases, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, No 37. Guoxue Alley, Chengdu, 610000, China.
Department of Respiratory and Critical Care Medicine, Frontiers Science Center for Disease-Related Molecular Network, Center of Precision Medicine, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, 610000, China.
Clin Epigenetics. 2024 Sep 19;16(1):133. doi: 10.1186/s13148-024-01743-6.
Epigenetic age accelerations (EAAs) are a promising new avenue of research, yet their investigation in subacute thyroiditis (SAT) remains scarce. Our study endeavors to fill this void by exploring the potential causal association between EAAs and SAT.
Our study utilized publicly available genome-wide association study (GWAS) data of European ancestry to conduct a bidirectional Mendelian randomization (MR) study. Five MR methods were employed to measure causal association between EAAs and SAT multiple analyses were utilized to perform quality control.
Our study evaluated causal association between SAT and four EAAs, included GrimAge acceleration (GrimAA), Hannum age acceleration (HannumAA), PhenoAge acceleration (PhenoAA), intrinsic epigenetic age acceleration (IEAA). Results showed that there is a significant causal association between PhenoAA and SAT (OR 1.109, 95% CI 1.000-1.228, p = 0.049, by IVW method). On the contrary, SAT was associated with IEAA (OR 0.933, 95% CI 0.884-0.984, p = 0.011, by IVW method; OR 0.938, 95% CI 0.881-0.998, p = 0.043, by weighted median method). Leave-one-out sensitivity analysis, heterogeneity test, pleiotropy test, and MR-PRESSO analysis provide good quality control.
The bidirectional MR analysis concluded that an increase in PhenoAA was correlated with a higher risk of SAT, indicating a potential causal relationship between PhenoAA and risk of SAT. Conversely, SAT was found to be closely associated with IEAA, suggesting that SAT may accelerate the aging process. Slowing down biological aging has emerged as a new research direction in curbing SAT.
表观遗传年龄加速（EAAs）是一个很有前途的新研究领域，但在亚急性甲状腺炎（SAT）中的研究仍然很少。我们的研究旨在通过探索 EAAs 与 SAT 之间的潜在因果关系来填补这一空白。
我们的研究利用了欧洲血统的全基因组关联研究（GWAS）数据进行了双向孟德尔随机化（MR）研究。采用了五种 MR 方法来衡量 EAAs 和 SAT 之间的因果关系，使用了多种分析方法进行质量控制。
我们的研究评估了 SAT 和四个 EAAs 之间的因果关系，包括 GrimAge 加速（GrimAA）、Hannum 年龄加速（HannumAA）、PhenoAge 加速（PhenoAA）、内在表观遗传年龄加速（IEAA）。结果表明，PhenoAA 与 SAT 之间存在显著的因果关系（OR 1.109，95%CI 1.000-1.228，p=0.049，IVW 法）。相反，SAT 与 IEAA 相关（OR 0.933，95%CI 0.884-0.984，p=0.011，IVW 法；OR 0.938，95%CI 0.881-0.998，p=0.043，加权中位数法）。单倍型缺失敏感性分析、异质性检验、多效性检验和 MR-PRESSO 分析提供了良好的质量控制。
双向 MR 分析得出结论，PhenoAA 的增加与 SAT 风险的增加相关，表明 PhenoAA 与 SAT 风险之间存在潜在的因果关系。相反，SAT 与 IEAA 密切相关，表明 SAT 可能加速衰老过程。减缓生物衰老已成为抑制 SAT 的一个新研究方向。
