Gao TianQi, Chen TianYang, Ai ChengLong, Gu Yan, Wang YunPeng, Zhou XiaoLing, Zhao ChangWei
Changchun University of Chinese Medicine, Changchun, China.
Department of Orthopedics, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, China.
Biol Trace Elem Res. 2025 Apr 7. doi: 10.1007/s12011-025-04611-3.
There is a clear relationship between osteoarthritis (OA) and micronutrients. Excessive accumulation of micronutrients may play a negative role in aggravating the symptoms of OA. This study aims to sort out the causal relationship between micronutrients (zinc, copper, magnesium, vitamins A, C, E, D, B6, and B12, folic acid, iron, carotene, selenium, calcium, and potassium) and OA. This study used Mendelian randomization (MR) to combining the causal relationship between micronutrients and the risk of OA. Micronutrient-related variants were extracted from a large-scale genome-wide association study (GWAS) database of circulating micronutrients in European populations. Outcome data were from the FINNGEN meta-analysis of OA in participants of European ancestry from the FinnGen Biobank in Finland. The primary analysis was performed using the inverse-variance weighted (IVW) method, and a series of sensitivity analyses and multi-dimensionality analyses were conducted to detect possible violations of the MR assumptions. This study used the IVW method to analyze the causal relationship between 15 micronutrients and OA. The results showed that copper (P = 0.535), selenium (P = 0.463), folic acid (P = 0.664), carotene (P = 0.706), potassium (P = 0.839), vitamin D (P = 0.941), vitamin C (P = 0.928), vitamin B12 (P = 0.859), iron (P = 0.496), vitamin E (P = 0.678), magnesium (P = 0.934), vitamin B6 (P = 0.027), calcium (P = 0.743), and vitamin A (P = 0.368) had no significant causal relationship with OA. Among them, vitamin B6 showed P < 0.05 in the pleiotropy test, indicating the presence of pleiotropy. In contrast, zinc exhibited a significant causal relationship with OA (P < 0.001, OR 95% CI = 1.044 [1.021-1.067]), with sensitivity analyses further validating the robustness and reliability of this finding. This study reveals a causal relationship between zinc and OA, identifying zinc as a risk factor for OA. It provides evidence of causality between zinc and OA, offering novel insights for clinical research, diagnosis, and treatment of OA.
骨关节炎（OA）与微量营养素之间存在明确的关系。微量营养素的过度积累可能在加重OA症状方面起负面作用。本研究旨在梳理微量营养素（锌、铜、镁、维生素A、C、E、D、B6、B12、叶酸、铁、胡萝卜素、硒、钙和钾）与OA之间的因果关系。本研究采用孟德尔随机化（MR）方法来结合微量营养素与OA风险之间的因果关系。与微量营养素相关的变异体是从欧洲人群循环微量营养素的大规模全基因组关联研究（GWAS）数据库中提取的。结局数据来自芬兰FinnGen生物银行中欧洲血统参与者的OA的FINNGEN荟萃分析。主要分析采用逆方差加权（IVW）方法，并进行了一系列敏感性分析和多维度分析以检测是否可能违反MR假设。本研究使用IVW方法分析了15种微量营养素与OA之间的因果关系。结果显示，铜（P = 0.535）、硒（P = 0.463）、叶酸（P = 0.664）、胡萝卜素（P = 0.706）、钾（P = 0.839）、维生素D（P = 0.941）、维生素C（P = 0.928）、维生素B12（P = 0.859）、铁（P = 0.496）、维生素E（P = 0.678）、镁（P = 0.934）、维生素B6（P = 0.027）、钙（P = 0.743）和维生素A（P = 0.368）与OA无显著因果关系。其中，维生素B6在多效性检验中显示P < 0.05，表明存在多效性。相比之下，锌与OA存在显著因果关系（P < 0.001，OR 95% CI = 1.044 [1.021 - 1.067]），敏感性分析进一步验证了这一发现的稳健性和可靠性。本研究揭示了锌与OA之间的因果关系，确定锌为OA的一个风险因素。它提供了锌与OA之间因果关系的证据，为OA的临床研究、诊断和治疗提供了新的见解。
