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Association of Genetic Variants Related to Serum Calcium Levels With Coronary Artery Disease and Myocardial Infarction
Karolinska Inst, Inst Environm Med, Unit Nutr Epidemiol, SE-17177 Stockholm, Sweden..
Univ Cambridge, MRC Biostat Unit, Cambridge, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.ORCID iD: 0000-0003-2815-1217
2017 (English)In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 318, no 4, 371-380 p.Article in journal (Refereed) Published
Abstract [en]

IMPORTANCE Serum calcium has been associated with cardiovascular disease in observational studies and evidence from randomized clinical trials indicates that calcium supplementation, which raises serum calcium levels, may increase the risk of cardiovascular events, particularly myocardial infarction.

OBJECTIVE To evaluate the potential causal association between genetic variants related to elevated serum calcium levels and risk of coronary artery disease (CAD) and myocardial infarction using mendelian randomization.

DESIGN, SETTING, AND PARTICIPANTS The analyses were performed using summary statistics obtained for single-nucleotide polymorphisms (SNPs) identified from a genome-wide association meta-analysis of serum calcium levels (N = up to 61 079 individuals) and from the Coronary Artery Disease Genome-wide Replication and Meta-analysis Plus the Coronary Artery Disease Genetics (CardiogramplusC4D) consortium's 1000 genomes-based genome-wide association meta-analysis (N = up to 184 305 individuals) that included cases (individuals with CAD andmyocardial infarction) and noncases, with baseline data collected from 1948 and populations derived from across the globe. The association of each SNP with CAD andmyocardial infarction was weighted by its association with serum calcium, and estimates were combined using an inverse-variance weighted meta-analysis.

EXPOSURES Genetic risk score based on genetic variants related to elevated serum calcium levels.

MAIN OUTCOMES AND MEASURES Co-primary outcomes were the odds of CAD and myocardial infarction.

RESULTS Among the mendelian randomized analytic sample of 184 305 individuals (60 801 CAD cases [approximately 70% with myocardial infarction] and 123 504 noncases), the 6 SNPs related to serum calcium levels and without pleiotropic associations with potential confounders were estimated to explain about 0.8% of the variation in serum calcium levels. In the inverse-variance weighted meta-analysis (combining the estimates of the 6 SNPs), the odds ratios per 0.5-mg/dL increase (about 1 SD) in genetically predicted serum calcium levels were 1.25 (95% CI, 1.08-1.45; P = .003) for CAD and 1.24 (95% CI, 1.05-1.46; P = .009) for myocardial infarction.

CONCLUSIONS AND RELEVANCE A genetic predisposition to higher serum calcium levels was associated with increased risk of CAD andmyocardial infarction. Whether the risk of CAD associated with lifelong genetic exposure to increased serum calcium levels can be translated to a risk associated with short-term to medium-term calcium supplementation is unknown.

Place, publisher, year, edition, pages
AMER MEDICAL ASSOC , 2017. Vol. 318, no 4, 371-380 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-332841DOI: 10.1001/jama.2017.8981ISI: 000406296700017PubMedID: 28742912OAI: oai:DiVA.org:uu-332841DiVA: diva2:1155738
Available from: 2017-11-09 Created: 2017-11-09 Last updated: 2017-11-09Bibliographically approved

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