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. 2025 Mar 8;24(1):38.
doi: 10.1186/s12937-025-01100-0.

Mendelian randomization of serum micronutrients and osteoarthritis risk: focus on zinc

Wenxing Zeng  1   2 , Enda Hong  3   2 , Wei Ye  4   2 , Luyao Ma  1   2 , Dejun Cun  1   2 , Feng Huang  1   5   2 , Ziwei Jiang  6   7   8
Affiliations

Mendelian randomization of serum micronutrients and osteoarthritis risk: focus on zinc

Wenxing Zeng et al. Nutr J. .

Abstract

Background: Osteoarthritis (OA) is an increasingly severe public health issue globally. Micronutrients are essential for maintaining normal physiological functions and metabolic balance; however, their relationship with OA is not fully understood.

Methods: This study aimed to evaluate the potential causal relationships between 15 key micronutrients and the risk of OA using both two-sample and multivariate Mendelian randomization approaches. We gathered data from a large prospective cohort of genome-wide association studies on these micronutrients and OA. Comprehensive Mendelian randomization analyses were conducted using inverse variance weighting, MR Egger, weighted median, weighted models, and simple models. Through multivariate analyses, factors such as BMI and strenuous exercise were controlled to assess the independent associations between zinc and OA risk.

Results: In the two-sample Mendelian randomization analysis, zinc was positively associated with OA risk (OR = 1.045, 95% CI: 1.009 to 1.082, P = 0.015). This association remained significant even after controlling for other confounding factors in multivariate analyses, indicating an independent effect of zinc. Other micronutrients, such as calcium, iron, and vitamin D, did not show significant associations with OA risk in this study.

Conclusion: This study provides new evidence of a positive association between the micronutrient zinc and the risk of OA, emphasizing the importance of considering micronutrients in osteoarthritis prevention and treatment strategies. Future research should further validate these findings and explore the specific biological mechanisms by which zinc influences the risk of osteoarthritis.

Keywords: Causality; Mendelian randomization; Micronutrients; Multivariate analysis; Osteoarthritis; Zinc.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Ethical approval was not required for this study involving human data, in accordance with local legislation and institutional requirements. Similarly, written informed consent to participate was not necessary from the participants or their legal guardians/next of kin, as per national legislation and institutional guidelines. These decisions were based on the fact that the study used de-identified, publicly available data sets where participants’ privacy and confidentiality are inherently protected. institutional requirements. Conflict of interest: The authors declare that this study was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
Mendelian randomisation (MR) design flowchart
Fig. 2
Fig. 2
Results of 15 micronutrients with OA MR analysis (IVW & WME)
Fig. 3
Fig. 3
Positive results in 15 micronutrients
Fig. 4
Fig. 4
Results of MR analyses of zinc versus OA, including (A) scatter plots, (B) forest plots, (C) leave-one-out method, (D) funnel plots
Fig. 5
Fig. 5
Results of five MR analyses between micronutrient zinc and OA
Fig. 6
Fig. 6
Multivariate MR analysis to correct for the confounding effects of BMI and strenuous sports on the effects of zinc and OA
See this image and copyright information in PMC

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