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Assessing Causality in Associations of Serum Calcium and Magnesium Levels With Heart Failure: A Two-Sample Mendelian Randomization Study
Karolinska Inst, Inst Environm Med, Unit Nutr & Cardiovasc Epidemiol, Stockholm, Sweden.
Karolinska Inst, Inst Environm Med, Unit Nutr & Cardiovasc Epidemiol, Stockholm, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Karolinska Inst, Inst Environm Med, Unit Nutr & Cardiovasc Epidemiol, Stockholm, Sweden.ORCID iD: 0000-0003-0118-0341
2019 (English)In: Frontiers in Genetics, ISSN 1664-8021, E-ISSN 1664-8021, Vol. 10, article id 1069Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA , 2019. Vol. 10, article id 1069
Keywords [en]
calcium, heart failure, magnesium, minerals, Mendelian randomization
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:uu:diva-397594DOI: 10.3389/fgene.2019.01069ISI: 000494683900001PubMedID: 31708976OAI: oai:DiVA.org:uu-397594DiVA, id: diva2:1372373
Funder
Swedish Research CouncilAvailable from: 2019-11-22 Created: 2019-11-22 Last updated: 2019-11-22Bibliographically approved

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