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Causal Effect of Serum Magnesium on Osteoporosis and Cardiometabolic Diseases.

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.

SUBMITTER: He B

PROVIDER: S-EPMC8681341 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Causal Effect of Serum Magnesium on Osteoporosis and Cardiometabolic Diseases.

He Bin B Xia Liang L Zhao Jinqiu J Yin Lifeng L Zhang Muzi M Quan Zhengxue Z Ou Yunsheng Y Huang Wei W

Frontiers in nutrition 20211203

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, <i>p</i> < 5 × 10<sup>-8</sup>) associated with serum magnesium concentrations were all used as instrumental variables ...[more]

PMID: 34926542

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Project description:BackgroundObservational studies have shown that vitamin D binding protein (DBP) levels, a key determinant of 25-hydroxy-vitamin D (25OHD) levels, and 25OHD levels themselves both associate with risk of disease. If 25OHD levels have a causal influence on disease, and DBP lies in this causal pathway, then DBP levels should likewise be causally associated with disease. We undertook a Mendelian randomization study to determine whether DBP levels have causal effects on common calcemic and cardiometabolic disease.Methods and findingsWe measured DBP and 25OHD levels in 2,254 individuals, followed for up to 10 y, in the Canadian Multicentre Osteoporosis Study (CaMos). Using the single nucleotide polymorphism rs2282679 as an instrumental variable, we applied Mendelian randomization methods to determine the causal effect of DBP on calcemic (osteoporosis and hyperparathyroidism) and cardiometabolic diseases (hypertension, type 2 diabetes, coronary artery disease, and stroke) and related traits, first in CaMos and then in large-scale genome-wide association study consortia. The effect allele was associated with an age- and sex-adjusted decrease in DBP level of 27.4 mg/l (95% CI 24.7, 30.0; n = 2,254). DBP had a strong observational and causal association with 25OHD levels (p = 3.2 × 10(-19)). While DBP levels were observationally associated with calcium and body mass index (BMI), these associations were not supported by causal analyses. Despite well-powered sample sizes from consortia, there were no associations of rs2282679 with any other traits and diseases: fasting glucose (0.00 mmol/l [95% CI -0.01, 0.01]; p = 1.00; n = 46,186); fasting insulin (0.01 pmol/l [95% CI -0.00, 0.01,]; p = 0.22; n = 46,186); BMI (0.00 kg/m(2) [95% CI -0.01, 0.01]; p = 0.80; n = 127,587); bone mineral density (0.01 g/cm(2) [95% CI -0.01, 0.03]; p = 0.36; n = 32,961); mean arterial pressure (-0.06 mm Hg [95% CI -0.19, 0.07]); p = 0.36; n = 28,775); ischemic stroke (odds ratio [OR] = 1.00 [95% CI 0.97, 1.04]; p = 0.92; n = 12,389/62,004 cases/controls); coronary artery disease (OR = 1.02 [95% CI 0.99, 1.05]; p = 0.31; n = 22,233/64,762); or type 2 diabetes (OR = 1.01 [95% CI 0.97, 1.05]; p = 0.76; n = 9,580/53,810).ConclusionsDBP has no demonstrable causal effect on any of the diseases or traits investigated here, except 25OHD levels. It remains to be determined whether 25OHD has a causal effect on these outcomes independent of DBP. Please see later in the article for the Editors' Summary.

Dataset Information

Causal Effect of Serum Magnesium on Osteoporosis and Cardiometabolic Diseases.

Publications

Causal Effect of Serum Magnesium on Osteoporosis and Cardiometabolic Diseases.

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