Abstract
Serum magnesium is associated with osteoporosis and cardiometabolic diseases, but their causal associations remain elusive. We used the two-sample Mendelian randomization (MR) study to explore the causal roles of serum magnesium on osteoporosis and cardiometabolic diseases by using the aggregated genome-wide association studies (GWASs). Six single-nucleotide polymorphisms (SNPs, p < 5 × 10−8) associated with serum magnesium concentrations were all used as instrumental variables. A genetic predisposition to higher serum magnesium concentrations was inversely associated with lower lumbar spine bone mineral density (BMD, beta-estimate: −1.982, 95% CI: −3.328 to −0.635, SE: 0.687, p = 0.004), which was further confirmed by multiple sensitivity analyses. There was limited evidence of associations between serum magnesium and type 2 diabetes, coronary artery disease, heart failure, and atrial fibrillation. This work provided strong evidence that genetically increased serum magnesium concentrations were causally associated with low lumbar spine BMD and suggested that serum magnesium concentrations may be crucial to prevent osteoporosis.
Highlights
Magnesium, the second most abundant intracellular cation, participates in many physiological processes in osteoporosis and cardiovascular function, such as vascular tone, endothelial function, glucose, and insulin metabolism [1,2,3]
We evaluated the causal effect of serum magnesium on forearm
According to the primary (IVW) analysis, serum magnesium demonstrated no causal effect on forearm BMD
Summary
The second most abundant intracellular cation, participates in many physiological processes in osteoporosis and cardiovascular function, such as vascular tone, endothelial function, glucose, and insulin metabolism [1,2,3]. Previous studies revealed the benefits of magnesium supplementation to improve endothelial function [7, 8] and reduce blood pressure [9, 10], arterial stiffness [11], and postoperative arrhythmias [12, 13]. Chronic inflammation has a strong association with the concentration of magnesium and osteoporosis [14,15,16,17]. The pathogenesis of cardiovascular diseases (e.g., coronary artery disease, heart failure, and atrial fibrillation) and type 2 diabetes are affected by chronic inflammation [18,19,20,21]. Osteoporosis and cardiometabolic diseases have a robust connection with pathogenesis, and this study aims to study the influence of serum magnesium concentrations for the prevention and treatment of osteoporosis and cardiometabolic diseases
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