title: The shared allelic architecture of adiponectin levels and coronary artery disease.
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 < 4.4 × 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 × 10(-7)).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Epidemiology, Biostatistics and Occupational Health, Jewish General Hospital, Lady Davis Institute, McGill University Montreal, Quebec H3T 1E2, Canada.
authors.forename: Zari
authors.initials: Z
authors.lastname: Dastani
authors.forename: Toby
authors.initials: T
authors.lastname: Johnson
authors.forename: Florian
authors.initials: F
authors.lastname: Kronenberg
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Nelson
authors.forename: Themistocles L
authors.initials: TL
authors.lastname: Assimes
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.forename: J Brent
authors.initials: JB
authors.lastname: Richards
mesh_terms: D052242:Adiponectin / Q000235:genetics*; D050154:Adiposity / Q000235:genetics*; D000483:Alleles; D050197:Atherosclerosis / Q000453:epidemiology / Q000235:genetics; D003324:Coronary Artery Disease / Q000453:epidemiology* / Q000235:genetics*; D030541:Databases, Genetic; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012307:Risk Factors
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin