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Health effects associated with serum calcium concentrations: evidence from MR-PheWAS analysis in UK Biobank

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Abstract

Summary

We conducted a phenome-wide Mendelian randomization analysis (MR-PheWAS) to survey health effects associated with high normal serum calcium. We found causal evidence for conditions related to renal function, bone and joint health, and cardiovascular risk. These conditions collectively suggest that tissue calcification may be a key mechanism through which serum calcium influences health.

Introduction

Calcium is essential for the normal functioning of the cardiovascular system, muscles, and nerves. In this MR-PheWAS study, we sought to capture the totality of health effects associated with high normal serum calcium.

Methods

We used data from up to 337,535 UK Biobank participants, and tested for associations between calcium genetic score (calcium-GS) and 925 disease outcomes, with follow-up analyses using complementary MR methods.

Results

Calcium-GS was robustly associated with serum calcium concentration (F statistics = 349). After multiple testing correction (P < 1.62E-4), we saw genetic evidence for an association between high serum calcium and urinary calculus (OR per 1 mg/dl 3.5, 95%CI 1.3–9.2), renal colic (9.1, 95%CI 2.5–33.5), and allergy/adverse effect of penicillin (2.2, 95%CI 1.5–3.3). Secondary analyses with independent replication from consortia meta-analyses suggested further effects on myocardial infarction and osteoarthrosis.

Conclusion

We found causal evidence for effects of high normal serum calcium with conditions related to renal function, bone and joint health, and cardiovascular risk, which may collectively reflect influences on tissue calcification and immune function.

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Funding

This study was funded by the Australian National Health and Medical Research Foundation (NHMRC), grant number 1123603.

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Authors and Affiliations

  1. Australian Center for Precision Health, University of South Australia Cancer Research Institute, GPO Box 2471, Adelaide, SA, 5001, Australia

    A. Zhou & E. Hyppönen

  2. School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia

    H. A. Morris

  3. Population, Policy and Practice, UCL Institute of Child Health, London, UK

    E. Hyppönen

  4. South Australian Health and Medical Research Institute, Adelaide, Australia

    E. Hyppönen

Author notes

  1. H.A. Morris is deceased. This paper is dedicated to his memory.

    • H. A. Morris
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  1. A. Zhou
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Correspondence to E. Hyppönen.

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Ethical approval

UK Biobank was approved by the National Information Governance Board for Health and Social Care and North West Multicentre Research Ethics Committee (11/NW/0382). The present study was conducted under application number 20175.

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Zhou, A., Morris, H.A. & Hyppönen, E. Health effects associated with serum calcium concentrations: evidence from MR-PheWAS analysis in UK Biobank. Osteoporos Int 30, 2343–2348 (2019). https://doi.org/10.1007/s00198-019-05118-z

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  • DOI: https://doi.org/10.1007/s00198-019-05118-z

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