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

A Zhou1, H A Morris2, E Hyppönen3,4,5

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

Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
|August 9, 2019
PubMed

Insights

High normal serum calcium is causally linked to kidney stones, bone issues, and heart disease risk. These findings suggest tissue calcification is a key pathway influencing health outcomes.

Area of Science:

  • Genetics and Human Health
  • Biochemistry and Metabolism
  • Epidemiology

Background:

  • Calcium is vital for cardiovascular, muscular, and nervous system function.
  • Understanding the full spectrum of health effects from high normal serum calcium is crucial.
  • This study utilizes a phenome-wide Mendelian randomization approach to investigate these effects.

Purpose of the Study:

  • To conduct a phenome-wide Mendelian randomization analysis (MR-PheWAS) to identify health consequences of high normal serum calcium.
  • To explore the causal relationships between genetically predicted serum calcium levels and a wide range of disease outcomes.
  • To elucidate potential underlying mechanisms, such as tissue calcification, linking serum calcium to disease.

Main Methods:

  • Utilized UK Biobank data from up to 337,535 participants.
  • Constructed a calcium genetic score (calcium-GS) to represent genetically influenced serum calcium levels.
  • Tested associations between calcium-GS and 925 disease outcomes, employing complementary Mendelian randomization methods and rigorous statistical correction.

Main Results:

  • The calcium-GS was strongly associated with serum calcium concentration (F-statistic = 349).
  • Significant genetic evidence linked high serum calcium to urinary calculus (OR=3.5), renal colic (OR=9.1), and allergy/adverse drug reactions (OR=2.2) after multiple testing correction (P < 1.62E-4).
  • Secondary analyses indicated potential associations with myocardial infarction and osteoarthrosis, supported by independent replication.

Conclusions:

  • Established causal evidence for high normal serum calcium impacting conditions related to renal function, bone and joint health, and cardiovascular risk.
  • These findings collectively point towards tissue calcification as a significant mechanism mediating the health effects of serum calcium.
  • Suggests potential influences on immune function as well, warranting further investigation.

Keywords:
Calcium genetic scoreMendelian randomizationPhenome-wideSerum calcium

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