Yu Yunfeng, Tong Keke, Deng Juan, Wu Jingyi, Yu Rong, Xiang Qin
School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, No.300, Xueshi Road, Changsha, 410208, China.
The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007, China.
Biol Trace Elem Res. 2025 Feb 18. doi: 10.1007/s12011-025-04548-7.
The role of micronutrients in autoimmune thyroiditis (AIT) has been controversial and lacks sufficient genetic evidence. This study aimed to assess the relationships between various micronutrients and AIT by Mendelian randomization (MR). The single nucleotide polymorphisms (SNPs) of micronutrients and AIT were acquired from IEU Open GWAS project and FinnGen, and were screened according to the basic assumptions of MR. Subsequently, inverse variance weighted was set as the primary tool for MR analysis, with weighted median, simple mode, MR-Egger, and weighted mode set as secondary tools. Next, the MR-Egger intercept was used to assess the horizontal pleiotropy of results. Finally, Cochran's Q test and sensitivity analysis were used to assess the heterogeneity and robustness of the results, respectively. MR analysis showed that vitamin B12 reduced genetic susceptibility to AIT by 83.6% (odds ratio 0.164, 95% confidence interval 0.030 to 0.910, p = 0.039), whereas magnesium, calcium, carotene, copper, folate, iron, potassium, selenium, zinc, vitamin A, vitamin B6, vitamin C, vitamin D, and vitamin E were not associated with genetic susceptibility to AIT (p ≥ 0.05). The MR-Egger intercept showed that these results had no horizontal pleiotropy (p ≥ 0.05). Cochran's Q test and sensitivity analysis showed that these results were not heterogeneous (p ≥ 0.05) and were robust. This study demonstrated that vitamin B12 reduced the risk of AIT, whereas other micronutrients were not associated with the risk of AIT. It provides a new genetic perspective on the pathogenesis of AIT and strengthens the evidence for vitamin B12 as a potential treatment for AIT.
微量营养素在自身免疫性甲状腺炎（AIT）中的作用一直存在争议，且缺乏充分的遗传学证据。本研究旨在通过孟德尔随机化（MR）评估各种微量营养素与AIT之间的关系。从IEU Open GWAS项目和芬兰基因库获取微量营养素和AIT的单核苷酸多态性（SNP），并根据MR的基本假设进行筛选。随后，将逆方差加权法作为MR分析的主要工具，加权中位数法、简单模式法、MR-Egger法和加权模式法作为次要工具。接下来，使用MR-Egger截距评估结果的水平多效性。最后，分别使用 Cochr an's Q检验和敏感性分析评估结果的异质性和稳健性。MR分析表明，维生素B12使AIT的遗传易感性降低了83.6%（优势比0.164，95%置信区间0.030至0.910，p = 0.039），而镁、钙、胡萝卜素、铜、叶酸、铁、钾、硒、锌、维生素A、维生素B6、维生素C、维生素D和维生素E与AIT的遗传易感性无关（p≥0.05）。MR-Egger截距表明这些结果无水平多效性（p≥0.05）。 Cochr an's Q检验和敏感性分析表明这些结果无异质性（p≥0.05）且稳健。本研究表明，维生素B12降低了AIT的风险，而其他微量营养素与AIT风险无关。它为AIT的发病机制提供了新的遗传学视角，并加强了维生素B12作为AIT潜在治疗方法的证据。
