观察性研究表明原发性硬化性胆管炎（PSC）与甲状腺功能障碍（TD）之间存在关联。然而，PSC 和 TD 之间的因果关系仍不确定。本研究的目的是调查这两种情况之间的因果关系和具体方向。深入了解 PSC 和 TD 之间的潜在因果关系对于阐明 PSC 的发病机制以及设计预防和治疗 PSC 及其相关并发症的创新方法非常有价值。我们进行了双向双样本孟德尔随机化 (MR) 分析研究PSC与TD之间的因果关系，例如自身免疫性甲状腺疾病（AITD）、甲状腺癌（TC）、促甲状腺激素（TSH）、促甲状腺激素释放激素（TRH）等。 PSC 是暴露变量，而 TD 是结果变量。为了确定合适的工具变量（IV），我们利用全基因组关联研究（GWAS）数据集来选择潜在的候选单核苷酸多态性（SNP）。采用的主要统计方法是逆方差加权（IVW）方法，并辅以一系列敏感性分析，通过估计异质性和多效性来评估结果的稳健性。我们发现遗传预测的 PSC 和 Graves 之间的因果关系疾病（GD）、甲状腺功能亢进（IVW OR=1.230，95%CI：1.089-1.389，P=0.001；IVW OR=1.001，95%CI：1.000-1.002，P=0.000）具有统计学意义。反向MR分析表明，甲状腺功能亢进（P=0.000）和甲状腺功能减退（p=0.028）的遗传易感性可能是PSC的危险因素。除通过双向两样本分析确定的 GD、甲状腺功能亢进和甲状腺功能减退症外，PSC 与其他 TD 之间没有观察到统计学上显着的因果关系（IVW P>0.05）。为了确保我们研究结果的可靠性，我们进行了额外的敏感性分析，包括留一法（LOO）检验、异质性检验和多效性检验。在这项研究中，我们对PSC和TD之间的因果关系进行了调查。我们的研究结果表明，从统计学角度来看，PSC 显着提高了 GD 和甲状腺功能亢进症的易感性。这些结果揭示了 PSC 的病因，并对 PSC 患者的治疗具有重要意义。版权所有 © 2023 张和郎。

Observational studies have demonstrated an association between primary sclerosing cholangitis (PSC) and thyroid dysfunction (TD). However, the causal relationship between PSC and TD remains uncertain. The purpose of this study is to investigate the causal associations and specific direction between these two conditions. Gaining insight into the potential causal relationship between PSC and TD is valuable for elucidating the pathogenesis of PSC and for devising innovative approaches for the prevention and treatment of PSC and its associated complications.We conducted a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal association between PSC and TD, such as autoimmune thyroid disease (AITD), thyroid cancer (TC), thyroid stimulating hormone (TSH), thyrotropin-releasing hormone (TRH), among others. PSC was the exposure variable, while TD was the outcome variable. To identify suitable instrumental variables (IVs), we utilized genome-wide association study (GWAS) datasets to select potential candidate single-nucleotide polymorphisms (SNPs). The primary statistical approach employed was the inverse-variance weighted (IVW) method, which was complemented by a series of sensitivity analyses to assess the robustness of the results by estimating heterogeneity and pleiotropy.We found that the causal associations between genetically predicted PSC and Graves' disease (GD), hyperthyroidism (IVW OR=1.230, 95%CI: 1.089-1.389, P=0.001; IVW OR=1.001, 95%CI: 1.000-1.002, P=0.000) were statistically significant. The reverse MR analysis indicated that genetic susceptibility to hyperthyroidism (P=0.000) and hypothyroidism (p=0.028) might be the risk of PSC. There was no statistically significant causal association observed between PSC and other TD (IVW P>0.05), with the exception of GD, hyperthyroidism, and hypothyroidism as determined through bidirectional two-sample analysis. To ensure the reliability of our findings, additional sensitivity analyses were conducted, including the leave-one-out (LOO) test, heterogeneity test, and pleiotropic test.In this study, we conducted an investigation into the causal association between PSC and TD. Our findings indicate that PSC significantly elevates the susceptibility to GD and hyperthyroidism from a statistical perspective. These results shed light on the etiology of PSC and have implications for the management of patients with PSC.Copyright © 2023 Zhang and Lang.