Causal Association Between 12 Micronutrients and Common Chronic Respiratory Diseases: A Bidirectional Two‐Sample Mendelian Randomization Study

<b>Background:</b> This study aims to investigate the causal relationships between 12 micronutrients and common chronic respiratory diseases, revealing whether these nutrients play a causative role in either preventing or exacerbating these conditions. <b>Methods:</b> We employed a bidirectional two-sample Mendelian randomization (MR) approach to explore the causal relationships between micronutrients and chronic respiratory diseases. Data were sourced from the IEU GWAS database, with micronutrients serving as exposure variables and chronic respiratory diseases as outcome variables for causal assessment. This was followed by reverse MR analysis, where the steps were reversed. Analytical methods included inverse-variance weighting (IVW), MR-Egger regression, and the weighted median method to correct for potential pleiotropy and reverse causality. Cochran's <i>Q</i> test and the MR-PRESSO method were used for pleiotropy tests to ensure robustness and reliability of the results. <b>Results:</b> The MR analysis revealed that the genetically predicted calcium is a protective factor for asthma (OR = 0.99, 95% CI 0.984-0.995, <i>p</i> < 0.01), vitamin B12 is a risk factor for asthma (OR = 1.015, 95% CI 1.005-1.024, <i>p</i> < 0.01), and vitamin E is a protective factor for idiopathic pulmonary fibrosis (IPF) (OR = 0.952, 95% CI 0.916-0.989, <i>p</i>=0.012). In the reverse MR analysis, asthma showed a potential causal relationship with calcium levels (OR = 0.829, 95% CI 0.704-0.976, <i>p</i>=0.025), while pneumoconiosis showed a potential risk causal relationship with calcium levels (OR = 1.003, 95% CI 1.002-1.004, <i>p</i> < 0.010). Additionally, pneumoconiosis was found to have a potential protective causal relationship with vitamin E levels (OR = 0.999, 95% CI 0.999-1.000, <i>p</i>=0.034), and sarcoidosis was found to have a potential protective causal relationship with vitamin B12 levels (OR = 0.989, 95% CI 0.979-1.000, <i>p</i>=0.044). <b>Conclusion:</b> This study shows significant causal associations among calcium, vitamin B12, and vitamin E with chronic respiratory diseases. There is a bidirectional protective causal relationship between calcium and asthma, suggesting that increasing calcium intake may reduce the risk of asthma. However, the causal relationships among other vitamins, minerals, and chronic respiratory diseases remain inconclusive, necessitating further research to validate these findings' robustness and generalizability.