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

Apr 8, 2025Biological trace element research

Possible Link Between Zinc Levels and Osteoarthritis Using Genetic Analysis

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Abstract

Zinc is associated with an increased risk of osteoarthritis (OA) with P < 0.001.

Micronutrients like copper, selenium, and vitamins A, C, D, E, and B12 did not show a significant causal relationship with OA.
Vitamin B6 indicated potential pleiotropy with P < 0.05, suggesting it may not have a straightforward causal effect on OA.
The analysis utilized to assess the causal relationships between 15 micronutrients and OA.
Data were sourced from a large genome-wide association study and the FINNGEN meta-analysis involving European ancestry participants.
Sensitivity analyses supported the reliability of the significant association between zinc and OA.

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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 (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.

Key numbers

1.044 [1.021-1.067]

Causal Association with OA

Odds Ratio (OR) with 95% Confidence Interval (CI)

< 0.001

Significance Level for Zinc

P-value indicating the association's reliability

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

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