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Nutrition in acute and chronic diseases

The association of serum magnesium and chronic kidney disease: a two-sample mendelian randomization study of European descent

Abstract

Background

Previous observational studies focused on the association of serum magnesium (SMg) and chronic kidney disease (CKD), but the conclusion was inconsistent. To investigate the causal relationship of SMg and CKD, we performed a two-sample mendelian randomization (TSMR) analysis using publicly datasets.

Method

In mendelian randomization (MR) analysis, we used single nucleotide polymorphisms (SNPs) which had genetic statistical significance with SMg but not associated with kidney function and confounding factors as instrumental variable (IV). To select SNPs, we used publicly database of Genome Wide Association Study (GWAS) and Chronic Kidney Disease Genetics (CKDGen) Confirms. We used inverse-variance weighted (IVW), weighted median, MR-Egger regression, weighted mode, and simple mode approaches in TSMR analysis.

Results

We selected 4 SNPs (rs4072037, rs7965584, rs11144134 and rs448378) as IV. In IVW approach, the result of MR analysis for CKD was OR = 0.55, 95% CI: 0.06, 4.75, P = 0.58; for estimated glomerular filtration rate from creatinine (eGFR)crea was β = −0.06, 95% CI: −1.08, 0.07, P = 0.39; for estimated glomerular filtration rate from cystatin C (eGFR)cys was β = −0.03, 95% CI: −0.43, 0.36, P = 0.86, respectively per SD increase in SMg. When subgroup by diabetes mellitus (DM), the results for DM-eGFRcrea was β = −0.33, 95% CI: −0.85, 0.19, P = 0.21; and for non-DM-eGFRcrea was β = −0.03, 95% CI: −0.16, 0.11, P = 0.71. The results of other four MR approaches were consistent with IVW approach (all P > 0.05).

Conclusion

Our TSMR analysis showed that SMg had no causal effect on kidney function and progress CKD in European descent. As for the results about overall population, the verified study is needed in future study.

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Fig. 1: Participant flow chart and analysis plan using MR.
Fig. 2: Diagram of the instrumental variable assumptions for the Mendelian randomization study.
Fig. 3: Association between genetically predicted SMg concentrations and CKD and kidney function and its subtypes.

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Data availability

All data generated or analyzed during this study are included in this published article and its additional files.

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Acknowledgements

We thank the TAGC, the CKDGen consortium, and the Drinking, Tobacco and Genetics consortium for access to their data.

Funding

Cultivation Project of Young Talents supported by Cancer Hospital of Shandong First Medical University (ID: CH-SFMU-QM20210006). Department of Science and Technology of Shandong Province (ID: 202112010746).

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The authors’ responsibilities were as follows—QH: designed the research; WX: revised the manuscript and designed the research; all authors: analyzed the data; CH, YW and XS: wrote and revised the paper; QH: had primary responsibility for final content; and all authors: read and approved the final manuscript.

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Correspondence to Wei Xin or Qingzhi Hou.

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Hou, C., Wang, Y., Sui, X. et al. The association of serum magnesium and chronic kidney disease: a two-sample mendelian randomization study of European descent. Eur J Clin Nutr 76, 1309–1314 (2022). https://doi.org/10.1038/s41430-022-01106-5

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