1. The shared allelic architecture of adiponectin levels and coronary artery disease
- Author
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Michael Preuss, Christopher Nelson, Marja-Liisa Nuotio, Peter P Pramstaller, Leo-Pekka Lyytikäinen, David Altshuler, Vilmundur Gudnason, Andrew Hicks, Andreas Ziegler, Hae-Won Uh, Zouhair Aherrahrou, Claudia Langenberg, Stavroula Kanoni, Terho Lehtimäki, Christie Ballantyne, Toby Johnson, Celia Greenwood, Cornelia Van Duijn, David Couper, Annette Peters, Pieternella Slagboom, Marian Beekman, Jeanette Erdmann, Robert Kenneth Semple, Aurelian Bidulescu, Christian Fuchsberger, Kati Kristiansson, Marcus Kleber, Tanja Zeller, Thomas Meitinger, Themistocles Assimes, Florian Kronenberg, Olle Melander, and Ingrid Meulenbelt
- Subjects
Male ,Genotype ,Multifunction cardiogram ,Single-nucleotide polymorphism ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,Biology ,Bioinformatics ,Polymorphism, Single Nucleotide ,Article ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Databases, Genetic ,Mendelian randomization ,Prevalence ,Humans ,SNP ,Genetic Predisposition to Disease ,Alleles ,Adiposity ,030304 developmental biology ,Genetic association ,0303 health sciences ,Framingham Risk Score ,Adiponectin ,Confounding ,Atherosclerosis ,Cardiology and Cardiovascular Medicine ,Genome-Wide Association Study - Abstract
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 ). 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 × 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.
- Published
- 2013
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