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Abstract：
Investigating the association between inflammatory cytokines and hypothyroidism remains challenging due to limitations in traditional observational studies. In this study, we employed Mendelian randomization (MR) to assess the causal relationship between 41 inflammatory cytokines and hypothyroidism.
Inflammatory cytokines in 30,155 individuals of European ancestry with hypothyroidism and in a GWAS summary containing 8,293 healthy participants were included in the study for bidirectional two-sample MR analysis. We utilized inverse variance weighting (IVW), weighted median (WM), and Mendelian randomization-Egger (MR-Egger) methods. Multiple sensitivity analyses, including MR-Egger intercept test, leave-one-out analysis, funnel plot, scatterplot, and MR-PRESSO, were applied to evaluate assumptions.
We found evidence of a causal effect of IL-7 and macrophage inflammatory protein-1β (MIP-1β) on the risk of hypothyroidism, and a causal effect of hypothyroidism on several cytokines, including granulocyte colony-stimulating factor (G-CSF), IL-13, IL-16, IL-2rα, IL-6, IL-7, IL-9, interferon-γ-inducible protein 10 (IP10), monokine induced by interferon (IFN)-γ (MIG), macrophage inflammatory protein-1β (MIP-1β), stem cell growth factors-β (SCGF-β), stromal cell derived factor-1α (SDF-1α), and tumor necrosis factor-α (TNF-α).
Our study suggests that IL-7 and MIP-1β may play a role in the pathogenesis of hypothyroidism, and that hypothyroidism may induce a systemic inflammatory response involving multiple cytokines. These findings may have implications for the prevention and treatment of hypothyroidism and its complications. However, further experimental studies are needed to validate the causal relationships and the potential of these cytokines as drug targets.
Inflammatory cytokines in 30,155 individuals of European ancestry with hypothyroidism and in a GWAS summary containing 8,293 healthy participants were included in the study for bidirectional two-sample MR analysis. We utilized inverse variance weighting (IVW), weighted median (WM), and Mendelian randomization-Egger (MR-Egger) methods. Multiple sensitivity analyses, including MR-Egger intercept test, leave-one-out analysis, funnel plot, scatterplot, and MR-PRESSO, were applied to evaluate assumptions.
We found evidence of a causal effect of IL-7 and macrophage inflammatory protein-1β (MIP-1β) on the risk of hypothyroidism, and a causal effect of hypothyroidism on several cytokines, including granulocyte colony-stimulating factor (G-CSF), IL-13, IL-16, IL-2rα, IL-6, IL-7, IL-9, interferon-γ-inducible protein 10 (IP10), monokine induced by interferon (IFN)-γ (MIG), macrophage inflammatory protein-1β (MIP-1β), stem cell growth factors-β (SCGF-β), stromal cell derived factor-1α (SDF-1α), and tumor necrosis factor-α (TNF-α).
Our study suggests that IL-7 and MIP-1β may play a role in the pathogenesis of hypothyroidism, and that hypothyroidism may induce a systemic inflammatory response involving multiple cytokines. These findings may have implications for the prevention and treatment of hypothyroidism and its complications. However, further experimental studies are needed to validate the causal relationships and the potential of these cytokines as drug targets.
摘要：
由于传统观察性研究的局限性，研究炎性细胞因子与甲状腺功能减退症之间的关联仍然具有挑战性。在这项研究中,我们采用孟德尔随机化(MR)评估41种炎性细胞因子与甲状腺功能减退症之间的因果关系.
■在30,155名欧洲血统的甲状腺功能减退症患者和包含8,293名健康参与者的GWAS摘要中的炎性细胞因子被纳入双向双样本MR分析研究。我们利用方差逆加权(IVW)，加权中位数(WM)，和孟德尔随机化-Egger(MR-Egger)方法。多重敏感性分析，包括MR-Egger截距测试，遗漏分析，漏斗图,散点图，和MR-PRESSO,用于评估假设。
■我们发现了IL-7和巨噬细胞炎性蛋白-1β（MIP-1β）对甲状腺功能减退症风险的因果关系的证据，以及甲状腺功能减退对几种细胞因子的因果效应，包括粒细胞集落刺激因子（G-CSF），IL-13，IL-16，IL-2Rα，IL-6、IL-7、IL-9、干扰素-γ诱导蛋白10(IP10)、干扰素（IFN）-γ（MIG）诱导的单核因子，巨噬细胞炎性蛋白-1β（MIP-1β），干细胞生长因子-β（SCGF-β），基质细胞衍生因子-1α(SDF-1α),和肿瘤坏死因子-α(TNF-α)。
■我们的研究表明，IL-7和MIP-1β可能在甲状腺功能减退症的发病机制中起作用，甲状腺功能减退症可能诱发涉及多种细胞因子的全身性炎症反应。这些发现可能对甲状腺功能减退症及其并发症的预防和治疗具有重要意义。然而,需要进一步的实验研究来验证因果关系以及这些细胞因子作为药物靶标的潜力。
■在30,155名欧洲血统的甲状腺功能减退症患者和包含8,293名健康参与者的GWAS摘要中的炎性细胞因子被纳入双向双样本MR分析研究。我们利用方差逆加权(IVW)，加权中位数(WM)，和孟德尔随机化-Egger(MR-Egger)方法。多重敏感性分析，包括MR-Egger截距测试，遗漏分析，漏斗图,散点图，和MR-PRESSO,用于评估假设。
■我们发现了IL-7和巨噬细胞炎性蛋白-1β（MIP-1β）对甲状腺功能减退症风险的因果关系的证据，以及甲状腺功能减退对几种细胞因子的因果效应，包括粒细胞集落刺激因子（G-CSF），IL-13，IL-16，IL-2Rα，IL-6、IL-7、IL-9、干扰素-γ诱导蛋白10(IP10)、干扰素（IFN）-γ（MIG）诱导的单核因子，巨噬细胞炎性蛋白-1β（MIP-1β），干细胞生长因子-β（SCGF-β），基质细胞衍生因子-1α(SDF-1α),和肿瘤坏死因子-α(TNF-α)。
■我们的研究表明，IL-7和MIP-1β可能在甲状腺功能减退症的发病机制中起作用，甲状腺功能减退症可能诱发涉及多种细胞因子的全身性炎症反应。这些发现可能对甲状腺功能减退症及其并发症的预防和治疗具有重要意义。然而,需要进一步的实验研究来验证因果关系以及这些细胞因子作为药物靶标的潜力。
