甲状腺功能障碍与斑秃之间的遗传关联：双向双样本孟德尔随机化研究

The genetic link between thyroid dysfunction and alopecia areata: a bidirectional two-sample Mendelian randomization study

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Frontiers in Endocrinology

影响因子:4.6

分区:医学3区 / 内分泌学与代谢3区

发表日期:2024

作者: Le Gao, Wenrui Li, Qiang Song, Hengxing Gao, Mingwei Chen

DOI: 10.3389/fendo.2024.1440941

摘要

尽管描述性研究已发现甲状腺功能障碍（TD）与斑秃（AA）之间存在关联，但两者之间的因果关系仍不清楚。本研究旨在探讨二者之间的因果关系及其具体方向。我们进行了大规模的双样本孟德尔随机化（MR）分析，以检验甲状腺功能障碍（如Graves病（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）与AA之间是否存在关联。甲状腺功能障碍和AA的全基因组关联研究（GWAS）总结统计数据来自IEU OpenGwas项目。以反向方差加权（IVW）方法为主要分析手段，评估TD与AA之间的因果关系，并辅以加权中位数法、MR-Egger、简单模和加权模。此外，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 比值比=1.396，95% CI 1.030-1.892，P=0.031）和甲状腺功能减退（IVW 比值比=1.431，95% CI 1.138-1.799，P=0.002）单核苷酸多态性（SNP）显著增加AA的风险。逆向MR分析表明，AA的遗传易感性（β=-0.029，95% CI -0.051 至 -0.007，P=0.009）可能是TRH的风险因素。正向MR分析未观察到其他TD与AA之间存在统计学显著的因果关系（IVW P>0.05）。逆向MR分析也未显示除TRH之外的其他TD与AA之间存在统计学显著关联（IVW P>0.05）。此外，还进行了包括留一法、异质性检验和多效性检验在内的多项敏感性分析，以评估结果的稳健性。本研究对TD与AA之间的因果关系进行了全面分析，为TD与斑秃之间的因果关系提供了有力的遗传证据，揭示了AA患者的某些病因，对于AA的管理和治疗具有重要意义。

Abstract

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.