Causal effect of serum magnesium on the risk of 9 respiratory diseases: a Mendelian randomization study

Abstract Objective: Although the association between serum magnesium and respiratory diseases has been explored, the causal effects of serum magnesium on respiratory diseases are largely unknown. Here we performed a Mendelian randomization(MR) analysis to investigate the association between serum magnesium concentrations and risk of 9 respiratory diseases. Methods: Mendelian randomization was conducted using single-nucleotide polymorphisms(SNPs) associated with serum magnesium as instrumental variables.To select SNPs, we used publicly available summary-level data from Genome-wide association studies (GWASs). We used inverse-variance weighted (IVW), weighted median, MR-Egger regression approaches in this analysis.The IVW method was used in the primary analysis to obtain the causal estimates. Results: Genetically predicted serum magnesium was inversely associated with the risk of asthma.The odds ratios in genetically predicted serum magnesium concentrations was 0.229 (95% confidence interval [CI] 0.065-0.806; p=0.022),which was further confirmed by multiple sensitivity analyses. Other diseases such as pulmonary embolism, lobar pneumonia, COVID-19, lung adenocarcinoma, lung squamous cell carcinoma, bronchiectasis, tuberculosis and interstitial lung disease did not yield statistically significant results. Conclusions : High genetically predicted serum magnesium was causally associated with a decreased risk of asthma and suggested that serum magnesium concentrations may be crucial to prevent the onset of asthma.