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Association of Genetic Variants Related to Serum Calcium Levels With Coronary Artery Disease and Myocardial
Susanna C Larsson1, Stephen Burgess2, Karl Michaëlsson3
1Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
JAMA
|July 26, 2017
Summary
Higher serum calcium levels, indicated by genetic predisposition, are linked to an increased risk of coronary artery disease (CAD) and myocardial infarction. Further research is needed to understand if this translates to risks from calcium supplementation.
Area of Science:
- Genetics
- Cardiovascular Medicine
- Epidemiology
Background:
- Observational studies suggest a link between serum calcium and cardiovascular disease (CVD).
- Randomized trials indicate calcium supplementation may elevate CVD event risk, particularly myocardial infarction.
- Mendelian randomization is a robust method to investigate causal relationships between exposures and outcomes.
Purpose of the Study:
- To assess the causal association between genetic variants for elevated serum calcium and the risk of coronary artery disease (CAD) and myocardial infarction.
- Utilize Mendelian randomization to explore genetic predispositions to serum calcium levels and their impact on cardiovascular health.
Main Methods:
- Employed Mendelian randomization using summary statistics from genome-wide association studies (GWAS) for serum calcium and CAD/myocardial infarction.
- Analyzed single-nucleotide polymorphisms (SNPs) associated with serum calcium levels and their association with CAD and myocardial infarction.
- Used inverse-variance weighted meta-analysis to combine SNP estimates and assess the causal effect.
Main Results:
- Six SNPs explained approximately 0.8% of serum calcium variation.
- A genetically predicted 0.5 mg/dL increase in serum calcium was associated with a 25% increased odds of CAD (OR, 1.25; P=.003).
- A similar increase was linked to a 24% higher odds of myocardial infarction (OR, 1.24; P=.009).
Conclusions:
- A genetic predisposition to higher serum calcium levels is causally associated with an increased risk of CAD and myocardial infarction.
- The long-term effects of genetically elevated calcium contrast with the unknown risks of short-term calcium supplementation.
- Findings highlight the importance of considering genetic factors in cardiovascular risk assessment.
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