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常见自身免疫性疾病与自身免疫性甲状腺炎的关联:一项两样本 Mendelian 随机化研究。

The association of common autoimmune diseases with autoimmune thyroiditis: a two-sample Mendelian randomization study.

机构信息

Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.

Department of Rheumatology, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.

出版信息

Front Endocrinol (Lausanne). 2024 Sep 9;15:1383221. doi: 10.3389/fendo.2024.1383221. eCollection 2024.

Abstract

OBJECTIVE

Numerous observational and retrospective studies have demonstrated an association between Autoimmune Thyroiditis (AIT) and various systemic Autoimmune Diseases (AIDs). However, the causal relationship between them remains uncertain. This study aims to investigate the causal link between AIT and diverse types of AIDs utilizing the Mendelian Randomization (MR) method.

METHOD

We assessed the causal relationship between AIT and eight prevalent AIDs. Summary statistics from genome-wide association studies (GWAS) were sourced from the FinnGen biobank and IEU Open GWAS database. Two-sample MR analyses were conducted, with the primary statistical approach being the Inverse Variance Weighting (IVW) method. This was complemented by a series of sensitivity analyses, and the robustness of the findings was evaluated through the estimation of heterogeneity and pleiotropy.

RESULTS

When AIT was considered as the outcome, MR evidence suggested an association between Rheumatoid arthritis (RA), Type 1 diabetes (T1D), and Systemic lupus erythematosus (SLE) with AIT. Utilizing the Inverse Variance Weighting (IVW) method, we observed an increased risk of AIT with exposure to RA ( = 0.024, OR=1.25; 95% CI = 1.03, 1.52), T1D ( < 0.001, OR=1.27 95% CI = 1.11,1.46), and SLE ( = 0.037, OR=1.14; 95% CI = 1.04,1.26). Conversely, no significant genetic causal relationship with AIT was found for Sjögren's syndrome (SS), Ankylosing Spondylitis (AS), Multiple sclerosis (MS), Crohn's disease (CD), and Ulcerative colitis (UC).

CONCLUSION

This study identified RA, T1D, and SLE as triggering factors for AIT. The incidence rate of AIT in patients with RA, T1D, and SLE may be higher than that in the general population. Therefore, individuals with these three diseases should undergo regular monitoring of thyroid-related indicators.

摘要

目的

大量观察性和回顾性研究表明自身免疫性甲状腺炎(AIT)与各种系统性自身免疫性疾病(AIDs)之间存在关联。然而,它们之间的因果关系仍不确定。本研究旨在利用孟德尔随机化(MR)方法研究 AIT 与多种类型的 AIDs 之间的因果关系。

方法

我们评估了 AIT 与八种常见 AIDs 之间的因果关系。从 FinnGen 生物库和 IEU 开放 GWAS 数据库中获取全基因组关联研究(GWAS)的汇总统计数据。进行了两样本 MR 分析,主要统计方法是逆方差加权(IVW)法。通过一系列敏感性分析对结果进行了补充,并通过评估异质性和多效性来评估结果的稳健性。

结果

当将 AIT 视为结局时,MR 证据表明类风湿性关节炎(RA)、1 型糖尿病(T1D)和系统性红斑狼疮(SLE)与 AIT 之间存在关联。使用逆方差加权(IVW)法,我们观察到暴露于 RA( = 0.024,OR=1.25;95%CI = 1.03,1.52)、T1D( < 0.001,OR=1.27 95%CI = 1.11,1.46)和 SLE( = 0.037,OR=1.14;95%CI = 1.04,1.26)时 AIT 的风险增加。相反,Sjögren 综合征(SS)、强直性脊柱炎(AS)、多发性硬化症(MS)、克罗恩病(CD)和溃疡性结肠炎(UC)与 AIT 之间没有发现显著的遗传因果关系。

结论

本研究确定 RA、T1D 和 SLE 是 AIT 的触发因素。RA、T1D 和 SLE 患者的 AIT 发生率可能高于普通人群。因此,这三种疾病的患者应定期监测与甲状腺相关的指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f577/11416997/4ef466c6e828/fendo-15-1383221-g001.jpg

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