Department of Dermatology, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, China.
Changzhi Medical College, Changzhi, China.
Skin Res Technol. 2024 Oct;30(10):e70063. doi: 10.1111/srt.70063.
Observational studies have suggested a correlation between alopecia areata (AA) and thyroid dysfunction (TD). However, the causal relationship between AA and TD remains uncertain. The purpose of this study is to investigate the causal relationship between these two conditions. Understanding the potential causal relationship between AA and TD is valuable for elucidating the pathogenesis of AA and for designing innovative methods to prevent and treat AA and its related complications.
All data for this two-sample Mendelian randomization (MR) study were sourced from public databases. This study selected hypothyroidism, Hashimoto's thyroiditis, hyperthyroidism, subacute thyroiditis, and Graves' disease as exposure factors, with AA as the outcome variable. Data for hypothyroidism, Hashimoto's thyroiditis, hyperthyroidism, subacute thyroiditis, Graves' disease, and AA were obtained from related genome-wide association studies (GWAS). Various MR analysis methods such as inverse variance weighted (IVW), MR-Egger, and weighted median were utilized. Additionally, Cochrane's Q test was used to detect heterogeneity in MR results, and the MR-Egger intercept test and MR pleiotropy residual sum and outlier (MR-PRESSO) test were used to detect horizontal pleiotropy. A leave-one-out analysis was conducted to investigate the sensitivity of this association.
We found statistically significant genetic predictions of AA with hypothyroidism, Hashimoto's thyroiditis, and subacute thyroiditis (IVW OR = 1.4009815, 95% confidence interval [CI]: 1.1210399-1.750829; p = 0.003030698, OR = 1.396101, 95% CI: 1.030134-1.89208; p = 0.03144273, OR = 0.732702, 95% CI: 0.604812-0.887634; p = 0.001483368). Furthermore, tests for pleiotropy showed no evidence of pleiotropy, enhancing the credibility of the study results. Finally, the leave-one-out test demonstrated the stability and robustness of this association.
This study provides new evidence of a potential genetic link between thyroid issues and AA. By employing the two-sample MR method to eliminate confounding factors and reverse causation, unbiased results were obtained, confirming a causal relationship between hypothyroidism, Hashimoto's thyroiditis, subacute thyroiditis, and AA. This lays the foundation for further mechanistic studies and potential clinical applications. Future research should further explore the specific biological mechanisms between TD and the onset of AA.
观察性研究表明斑秃（AA）与甲状腺功能障碍（TD）之间存在相关性。然而，AA 和 TD 之间的因果关系仍不确定。本研究旨在探讨这两种情况之间的因果关系。了解 AA 和 TD 之间潜在的因果关系对于阐明 AA 的发病机制以及设计预防和治疗 AA 及其相关并发症的创新方法具有重要意义。
本两项样本 Mendelian 随机化（MR）研究的数据均来自公共数据库。本研究选择甲状腺功能减退症、桥本甲状腺炎、甲状腺功能亢进症、亚急性甲状腺炎和格雷夫斯病作为暴露因素，以 AA 作为结局变量。甲状腺功能减退症、桥本甲状腺炎、甲状腺功能亢进症、亚急性甲状腺炎、格雷夫斯病和 AA 的数据来自相关的全基因组关联研究（GWAS）。使用各种 MR 分析方法，如逆方差加权（IVW）、MR-Egger 和加权中位数。此外，还使用 Cochrane's Q 检验检测 MR 结果的异质性，并使用 MR-Egger 截距检验和 MR 多效性残差和异常值（MR-PRESSO）检验检测水平多效性。进行了一项单样本剔除分析，以调查该关联的敏感性。
我们发现 AA 与甲状腺功能减退症、桥本甲状腺炎和亚急性甲状腺炎之间存在统计学上显著的遗传预测（IVW OR=1.4009815，95%置信区间[CI]：1.1210399-1.750829；p=0.003030698，OR=1.396101，95%CI：1.030134-1.89208；p=0.03144273，OR=0.732702，95%CI：0.604812-0.887634；p=0.001483368）。此外，多效性检验未发现多效性证据，增强了研究结果的可信度。最后，单样本剔除测试表明该关联具有稳定性和稳健性。
本研究提供了甲状腺问题与 AA 之间潜在遗传联系的新证据。通过采用两样本 MR 方法消除混杂因素和反向因果关系，得出了无偏倚的结果，证实了甲状腺功能减退症、桥本甲状腺炎、亚急性甲状腺炎与 AA 之间存在因果关系。这为进一步的机制研究和潜在的临床应用奠定了基础。未来的研究应进一步探索 TD 与 AA 发病之间的具体生物学机制。
