GWAS for discovery and replication of genetic loci associated with sudden cardiac arrest in patients with coronary artery disease

  • B.E. A
  • E. V
  • S.L. M
 et al. 
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Abstract

Background: Epidemiologic evidence suggests a heritable component to risk for sudden cardiac arrest independent of risk for myocardial infarction. Recent candidate gene association studies for community sudden cardiac arrests have focused on a limited number of biological pathways and yielded conflicting results. We sought to identify novel gene associations for sudden cardiac arrest in patients with coronary artery disease by performing a genome-wide association study.Methods: Tagging SNPs (n = 338,328) spanning the genome were typed in a case-control study comparing 89 patients with coronary artery disease and sudden cardiac arrest due to ventricular tachycardia or ventricular fibrillation to 520 healthy controls.Results: Fourteen SNPs including 7 SNPs among 7 genes (ACYP2, AP1G2, ESR1, DGES2, GRIA1, KCTD1, ZNF385B) were associated with sudden cardiac arrest (all p < 1.30 × 10-7), following Bonferroni correction and adjustment for population substructure, age, and sex; genetic variation in ESR1 (p = 2.62 × 10-8; Odds Ratio [OR] = 1.43, 95% confidence interval [CI]:1.277, 1.596) has previously been established as a risk factor for cardiovascular disease. In tandem, the role of 9 genes for monogenic long QT syndrome (LQT1-9) was assessed, yielding evidence of association with CACNA1C (LQT8; p = 3.09 × 10-4; OR = 1.18, 95% CI:1.079, 1.290). We also assessed 4 recently published gene associations for sudden cardiac arrest, validating NOS1AP (p = 4.50 × 10-2, OR = 1.15, 95% CI:1.003, 1.326), CSMD2 (p = 6.6 × 10-3, OR = 2.27, 95% CI:1.681, 2.859), and AGTR1 (p = 3.00 × 10-3, OR = 1.13, 95% CI:1.042, 1.215).Conclusion: We demonstrate 11 gene associations for sudden cardiac arrest due to ventricular tachycardia/ventricular fibrillation in patients with coronary artery disease. Validation studies in independent cohorts and functional studies are required to confirm these associations. © 2011 Aouizerat et al; licensee BioMed Central Ltd.

Author-supplied keywords

  • acylphosphatase
  • adaptin
  • age
  • aged
  • article
  • cardiovascular disease
  • case control study
  • controlled study
  • coronary artery disease
  • enzyme
  • estrogen receptor
  • female
  • gender
  • gene function
  • gene locus
  • genetic association
  • genetic variability
  • glutamate receptor 1
  • heart arrest
  • heart ventricle fibrillation
  • heart ventricle tachycardia
  • human
  • long QT syndrome
  • major clinical study
  • male
  • population structure
  • potassium channel
  • priority journal
  • protein
  • risk factor
  • single nucleotide polymorphism
  • sphingolipid enzyme
  • unclassified drug
  • zinc finger protein

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Authors

  • Aouizerat B.E.

  • Vittinghoff E.

  • Musone S.L.

  • Pawlikowska L.

  • Kwok P.-Y.

  • Olgin J.E.

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