Journal
ATHEROSCLEROSIS
Volume 229, Issue 1, Pages 145-148Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2013.03.034
Keywords
Adiponectin; Coronary artery disease; Atherosclerosis; Gene; Association; SNP
Funding
- Canadian Foundation for Innovation
- Canadian Institutes of Health Research (CIHR)
- Fonds de la recherche en sante du Quebec
- Lady Davis Institute
- Jewish General Hospital
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Objective: A large body of epidemiologic data strongly suggests an association between excess adiposity and coronary artery disease (CAD). Low adiponectin levels, a hormone secreted only from adipocytes, have been associated with an increased risk of CAD in observational studies. However, these associations cannot clarify whether this relationship is causal or due to a shared set of causal factors or even confounding. Genome-wide association studies have identified common variants that influence adiponectin levels, providing valuable tools to examine the genetic relationship between adiponectin and CAD. Methods: Using 145 genome wide significant SNPs for adiponectin from the ADIPOGen consortium (n = 49,891), we tested whether adiponectin-decreasing alleles influenced risk of CAD in the CARDIoGRAM consortium (n = 85,274). Results: In single-SNP analysis, 5 variants among 145 SNPs were associated with increased risk of CAD after correcting for multiple testing (P < 4.4 x 10(-4)). Using a multi-SNP genotypic risk score to test whether adiponectin levels and CAD have a shared genetic etiology, we found that adiponectin-decreasing alleles increased risk of CAD (P = 5.4 x 10(-7)). Conclusion: These findings demonstrate that adiponectin levels and CAD have a shared allelic architecture and provide rationale to undertake a Mendelian randomization studies to understand if this relationship is causal. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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