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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.01069

Assessing Causality in Associations of Serum Calcium and Magnesium Levels with Heart Failure: A Two-Sample Mendelian Randomization Study

 Emilie Helte1, Agneta Åkesson1 and  Susanna C. Larsson1, 2*
  • 1Karolinska Institute (KI), Sweden
  • 2Uppsala University, Sweden

Evidence from observational studies suggests that increased exposure to calcium may increase the risk of coronary heart disease and stroke whereas magnesium might have a protective effect on disease risk. However, studies of the associations of these minerals with heart failure are scarce and limited by potential biases introduced by confounding and reverse causality. We applied a two-sample Mendelian randomization design using summary estimates to assess whether serum calcium and magnesium concentrations are causally associated with heart failure. Summary statistics data were collected for seven and six single-nucleotide polymorphisms associated with calcium and magnesium, respectively, from the hitherto largest genome-wide association studies on these minerals. Corresponding summary statistics for genetic associations with heart failure were available from publicly available data based on the UK Biobank study and based on participants of European ancestry. The findings showed that neither serum calcium nor magnesium concentrations were associated with heart failure. In the standard inverse-variance weighted analysis, the odds ratios of heart failure per genetically predicted one standard deviation increase in mineral concentrations were 0.89 (95% confidence interval 0.67-1.17; p=0.41) for serum calcium and 0.89 (95% confidence interval 0.72-1.10; p=0.28) for serum magnesium. Results were robust in sensitivity analyses, including the weighted median and Mendelian randomization Egger analyses. In conclusion, these findings do not support previous findings suggesting a link between serum calcium and magnesium and heart failure, but this study was underpowered to detect weak associations.

Keywords: Calcium, Magnesium, Heart failiure, Mendelian randomization, Minerals

Received: 17 Jun 2019; Accepted: 04 Oct 2019.

Copyright: © 2019 Helte, Åkesson and Larsson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Susanna C. Larsson, Karolinska Institute (KI), Solna, Sweden,