Mineral Nutrition and the Risk of Chronic Diseases: A Mendelian Randomization Study

We applied Mendelian randomization analyses to investigate the potential causality between blood minerals (calcium, magnesium, iron, copper, and zinc) and osteoporosis (OP), gout, rheumatoid arthritis (RA), type 2 diabetes (T2D), Alzheimer's disease (AD), bipolar disorder (BD), schizophrenia , Parkinson's disease and major depressive disorder. Single nucleotide polymorphisms (SNPs) that are independent (r² < 0.01) and are strongly related to minerals (p < 5 × 10-8) are selected as instrumental variables. Each standard deviation increase in magnesium (0.16 mmol/L) is associated with an 8.94-fold increase in the risk of RA (p = 0.044) and an 8.78-fold increase in BD (p = 0.040) but a 0.10 g/cm² increase in bone density related to OP (p = 0.014). Each per-unit increase in copper is associated with a 0.87-fold increase in the risk of AD (p = 0.050) and BD (p = 0.010). In addition, there is suggestive evidence that calcium is positively correlated (OR = 1.36, p = 0.030) and iron is negatively correlated with T2D risk (OR = 0.89, p = 0.010); both magnesium (OR = 0.26, p = 0.013) and iron (OR = 0.71, p = 0.047) are negatively correlated with gout risk. In the sensitivity analysis, causal estimation is not affected by pleiotropy. This study supports the long-standing hypothesis that magnesium supplementation can increase RA and BD risks and decrease OP risk and that copper intake can reduce AD and BD risks. This study will be helpful to address some controversial debates on the relationships between minerals and chronic diseases.