The Causal Relationship Between Zinc and Osteoarthritis: A Two-Sample Mendelian Randomization Study

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.