The School of Clinical Medicine, Fujian Medical University, Fuzhou, China.
Department of General Surgery, Zhongshan Hospital, Xiamen University, Xiamen, China.
Front Immunol. 2024 Aug 20;15:1425351. doi: 10.3389/fimmu.2024.1425351. eCollection 2024.
Micronutrients play pivotal roles in modulating various aspects of the immune response. However, the existing literature on the association between micronutrients and autoimmune thyroiditis (AIT) remains limited and contentious. To address this gap, we conducted Mendelian randomization (MR) to investigate potential links between genetically predicted concentrations of six micronutrients (Copper (Cu), Iron (Ir), Calcium (Ca), Vitamin D (VD), Vitamin C (VC), Zinc (Zn)) and the risk of AIT.
Utilizing summary statistics from genome-wide association studies (GWAS) in individuals of European descent, we employed MR methodologies to elucidate the interplay between micronutrients and AIT. Three distinct MR techniques were employed: Inverse Variance Weighted (IVW), MR-Egger regression, and Weighted Median Estimator (WME). Additionally, we evaluated outcome heterogeneity using Cochran's Q statistic and assessed pleiotropy using the MR-Egger intercept.
IVW analysis revealed no substantial evidence supporting a significant impact of genetically predicted micronutrient concentrations on AIT risk (Cu: OR = 0.918, P = 0.875; Ir: OR = 0.653, P = 0.264; Ca: OR = 0.964, P = 0.906; VD: OR = 0.717, P = 0.378; VC: OR = 0.986, P = 0.875; Zn: OR = 0.789, P = 0.539). Cochran's Q test for IVW indicated no notable heterogeneity. Moreover, the MR-Egger intercept method suggested the presence of horizontal pleiotropy between serum VC levels and AIT (MR-Egger intercept = -0.037, p = 0.026), while no such pleiotropy was observed for other micronutrients.
Our MR analysis does not support a causal relationship between genetically predicted concentrations of six micronutrients (Cu, Ir, Ca, VD, VC, and Zn) and the risk of AIT.
微量营养素在调节免疫反应的各个方面起着关键作用。然而,关于微量营养素与自身免疫性甲状腺炎(AIT)之间的关联,现有文献仍然有限且存在争议。为了解决这一差距,我们进行了孟德尔随机化(MR)研究,以调查六种微量营养素(铜(Cu)、铁(Ir)、钙(Ca)、维生素 D(VD)、维生素 C(VC)、锌(Zn))的遗传预测浓度与 AIT 风险之间的潜在联系。
利用欧洲血统个体的全基因组关联研究(GWAS)的汇总统计数据,我们采用 MR 方法来阐明微量营养素与 AIT 之间的相互作用。使用了三种不同的 MR 技术:逆方差加权(IVW)、MR-Egger 回归和加权中位数估计(WME)。此外,我们使用 Cochran's Q 统计量评估了结果的异质性,并使用 MR-Egger 截距评估了多效性。
IVW 分析没有发现遗传预测的微量营养素浓度对 AIT 风险有显著影响的实质性证据(Cu:OR = 0.918,P = 0.875;Ir:OR = 0.653,P = 0.264;Ca:OR = 0.964,P = 0.906;VD:OR = 0.717,P = 0.378;VC:OR = 0.986,P = 0.875;Zn:OR = 0.789,P = 0.539)。IVW 的 Cochran's Q 检验表明没有明显的异质性。此外,MR-Egger 截距方法表明血清 VC 水平与 AIT 之间存在水平多效性(MR-Egger 截距= -0.037,p = 0.026),而其他微量营养素则没有观察到这种多效性。
我们的 MR 分析不支持六种微量营养素(Cu、Ir、Ca、VD、VC 和 Zn)的遗传预测浓度与 AIT 风险之间存在因果关系。