尽管描述性研究发现甲状腺功能障碍（TD）与斑秃（AA）之间存在关联，但 TD 与 AA 之间的因果关系仍不清楚。本研究的目的是调查两者之间的因果关系以及具体方向。我们进行了大规模、两个样本的孟德尔随机化 (MR) 分析，以检查 TD（例如格雷夫斯病 (Graves’isease) GD）、桥本甲状腺炎（HT）、甲状腺癌（TC）、促甲状腺激素（TSH）、促甲状腺激素释放激素（TRH）等）和AA。 TD 和 AA 的全基因组关联研究 (GWAS) 摘要统计数据来自 IEU OpenGwas 项目。以逆方差加权（IVW）法作为评价TD与AA之间因果关系的主要分析方法，辅以加权中位数、MR-Egger、简单模式和加权模式。此外，还进行了敏感性分析以评估研究结果的可靠性。我们的研究发现，HT（IVW OR = 1.396，95% CI 1.030-1.892，P=0.031）和甲状腺功能减退症（IVW OR = 1.396，95% CI 1.030-1.892，P=0.031）中的单核苷酸多态性（SNP） = 1.431, 95% CI 1.138-1.799, P=0.002) 显着增加 AA 风险。反向MR分析表明，对AA的遗传易感性（β=-0.029，95%CI=-0.051至-0.007，P=0.009）可能是TRH的风险。阳性MR分析观察到其他TD与AA之间没有统计学上显着的因果关系（IVW P>0.05）。反向 MR 分析还显示，除 TRH 之外，AA 与其他 TD (IVW P>0.05) 之间没有统计学显着相关性。此外，还进行了额外的敏感性分析，包括留一检验、异质性检验和多效性检验，以评估结果的稳健性。这项研究对 TD 和 AA 之间的因果关系进行了非常全面的分析，提供令人信服的遗传证据支持 TD 与斑秃之间的因果关系。揭示了AA患者的一些病因，对于AA患者的管理和治疗具有重要意义。版权所有©2024高、李、宋、高、陈。

Although descriptive studies have found an association between thyroid dysfunction (TD) and alopecia areata (AA), however, the causal relationship between TD and AA remains unclear. The purpose of this study is to investigate the causal relationship between the two and the specific directions.We performed large-scale, two-sample Mendelian randomization (MR) analyses to examine whether there was an association between TD (such as Graves' disease (GD), Hashimoto's thyroiditis (HT), thyroid cancer (TC), thyroid stimulating hormone (TSH), thyrotropin-releasing hormone (TRH), etc.) and AA. Genome-wide association study (GWAS) summary statistics for TD and AA were from the IEU OpenGwas project. The inverse variance-weighted (IVW) method was used as the primary analysis method to evaluate the causality between TD and AA, supplemented by the weighted median, MR-Egger, simple mode and weighted mode. In addition, sensitivity analyses were performed to assess the reliability of the study results.Our study found that single nucleotide polymorphisms (SNPs) in HT (IVW OR = 1.396, 95% CI 1.030-1.892, P=0.031) and hypothyroidism (IVW OR = 1.431, 95% CI 1.138-1.799, P=0.002) significantly increased the risk of AA. Reverse MR analysis indicated that genetic susceptibility to AA (β=-0.029, 95%CI=-0.051 to -0.007, P=0.009) may be a risk for TRH. Positive MR analysis observed no statistically significant causal relationship between other TD and AA (IVW P>0.05). Reverse MR analysis also showed no statistically significant association between AA and other TD (IVW P>0.05) other than TRH. Furthermore, additional sensitivity analyses were performed, including a leave-one-out test, a heterogeneity test, and a pleiotropy test to assess the robustness of the results.This study provides a very comprehensive analysis of the causal relationship between TD and AA, providing convincing genetic evidence to support the causal relationship between TD and alopecia areata. It reveals some causes of AA patients, which is of great significance for the management and treatment of AA patients.Copyright © 2024 Gao, Li, Song, Gao and Chen.