Huang Xianjun, Mao Mingqiu, Guo Tianhong, Wu Yuqin, Xu Qi, Dai Junliang, Huang Yuanshuai
Department of Clinical Medicine, Southwest Medical University, Luzhou, China,
Department of Clinical Medicine, Southwest Medical University, Luzhou, China.
Ann Nutr Metab. 2024;80(6):295-306. doi: 10.1159/000539610. Epub 2024 Jun 10.
Given the clinical association between thyroid dysfunction and iron deficiency anemia (IDA), as well as their shared association with iron status, this study aimed to investigate the causal relationship between iron status and thyroid dysfunction, while also examining the risk of IDA in relation to thyroid dysfunction.
A two-sample mendelian randomization (MR) study was conducted to identify the causal relationship of iron status on thyroid dysfunction, as well as thyroid dysfunction on IDA. Large-scale European population-based genome-wide association study databases were utilized (Genetics of Iron Status consortium, ThyroidOmics consortium, FinnGen consortium, and UK Biobank). Inverse variance-weighted (IVW) was used as the main analysis. In addition, we used weighted median and MR-Egger to enhance the robustness. Sensitivity analysis was conducted to evaluate the robustness of MR results.
The IVW estimates did not reveal any significant causal relationship between serum iron status markers and thyroid dysfunction. However, a significant causal relationship was observed between hypothyroidism and IDA (odds ratio [OR] = 1.101, 95% confidence interval [CI] = 1.048-1.157, p < 0.001). Repeated analyses also demonstrated a similar trend (OR = 1.023, 95% CI = 1.011-1.035, p < 0.001). Sensitivity analysis supported that the MR estimates were robust.
In our MR study, an upregulation of the hypothyroidism-associated gene was found to be significantly associated with an elevated risk of IDA in the European population. These findings may offer novel therapeutic insights for clinicians managing patients with hypothyroidism, IDA, or their comorbidities.
鉴于甲状腺功能障碍与缺铁性贫血（IDA）之间的临床关联，以及它们与铁状态的共同关联，本研究旨在探讨铁状态与甲状腺功能障碍之间的因果关系，同时研究与甲状腺功能障碍相关的IDA风险。
进行了一项两样本孟德尔随机化（MR）研究，以确定铁状态对甲状腺功能障碍以及甲状腺功能障碍对IDA的因果关系。利用了大规模的基于欧洲人群的全基因组关联研究数据库（铁状态遗传学联盟、甲状腺组学联盟、芬兰基因组联盟和英国生物银行）。采用逆方差加权（IVW）作为主要分析方法。此外，我们使用加权中位数和MR-Egger方法来增强稳健性。进行敏感性分析以评估MR结果的稳健性。
IVW估计未显示血清铁状态标志物与甲状腺功能障碍之间存在任何显著的因果关系。然而，观察到甲状腺功能减退与IDA之间存在显著的因果关系（优势比[OR]=1.101，95%置信区间[CI]=1.048-1.157，p<0.001）。重复分析也显示了类似的趋势（OR=1.023，95%CI=1.011-1.035，p<0.001）。敏感性分析支持MR估计是稳健的。
在我们的MR研究中，发现欧洲人群中甲状腺功能减退相关基因的上调与IDA风险升高显著相关。这些发现可能为临床医生管理甲状腺功能减退、IDA或其合并症患者提供新的治疗思路。
