甲状腺功能障碍与脱发Areata之间的遗传联系：双向孟德尔随机研究
The genetic link between thyroid dysfunction and alopecia areata: a bidirectional two-sample Mendelian randomization study
影响因子:4.60000
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
摘要
尽管描述性研究发现甲状腺功能障碍（TD）与脱发（AA）之间存在关联，但是TD与AA之间的因果关系尚不清楚。 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激素（TRH）等）和AA。 TD和AA的全基因组协会研究（GWAS）摘要统计数据来自IEU OpenGWAS项目。逆差异加权（IVW）方法用作评估TD和AA之间因果关系的主要分析方法，并补充了加权中位数，MR-EGGER，简单模式和加权模式。此外，进行了敏感性分析以评估研究结果的可靠性。 AA的风险。反向MR分析表明，对AA的遗传敏感性（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和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以外，AA与其他TD（IVW P> 0.05）之间没有统计学意义的关联。此外，还进行了其他敏感性分析，包括一项外出测试，异质性测试和多效性测试，以评估结果的鲁棒性。这项研究提供了非常全面的TD与AA因果关系的分析，对TD与AA之间的因果关系，提供令人信服的遗传证据，以支持TDD和Alopecia areata Areata AreaTa之间的因果关系。它揭示了AA患者的一些原因，这对于AA患者的管理和治疗至关重要。
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.