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

Area of Science:

• Nutritional Science
• Genetics
• Epidemiology

Background:

• Osteoarthritis (OA) is a degenerative joint disease with complex etiology.
• Micronutrient imbalances, particularly excessive accumulation, may exacerbate OA symptoms.
• Understanding the causal links between specific micronutrients and OA is crucial for effective management.

Purpose of the Study:

• To investigate the causal relationship between 15 key micronutrients and the risk of developing osteoarthritis (OA).
• To identify specific micronutrients that may act as risk factors or protective agents in OA pathogenesis.

Main Methods:

• Employed Mendelian randomization (MR) analysis, a robust genetic epidemiological approach.
• Utilized large-scale genome-wide association study (GWAS) data for micronutrient-related genetic variants in European populations.
• Integrated OA outcome data from the FinnGen meta-analysis.

Main Results:

• Zinc was identified as having a significant causal relationship with OA (P < 0.001), indicating it as a risk factor.
• No significant causal relationships were found between OA and copper, selenium, folic acid, carotene, potassium, vitamin D, vitamin C, vitamin B12, iron, vitamin E, magnesium, vitamin B6, calcium, or vitamin A.
• Sensitivity analyses confirmed the robustness of the findings regarding zinc's association with OA.

Conclusions:

• Zinc emerges as a significant causal risk factor for osteoarthritis.
• The study provides strong evidence supporting a direct link between zinc levels and OA risk.
• These findings offer valuable insights for future clinical research, diagnostic strategies, and therapeutic interventions for OA.