title: Common variants in CASQ2, GPD1L, and NOS1AP are significantly associated with risk of sudden death in patients with coronary artery disease.
abstract: BACKGROUND
  Recent evidence suggests a genetic component for sudden cardiac death (SCD) in subjects with coronary artery disease (CAD). We conducted a systematic candidate-gene approach using haplotype-tagging single nucleotide polymorphisms (htSNPs) to identify genes associated with SCD risk in the context of CAD.
  
  
  RESULTS
  We investigated 1424 htSNPs representing 18 genes with mutations described in patients with ventricular arrhythmias in 291 subjects from the Oregon Sudden Unexpected Death Study (Ore-SUDS). The Ore-SUDS is an ongoing prospective investigation of SCD in the Portland, OR, metropolitan area (population, 1 000 000). SCD cases were ascertained from multiple sources and medical records were reviewed to determine the presence of CAD. A total of 36 SNPs were associated with risk of SCD (uncorrected probability values <0.01) in the initial study sample. These SNPs were subsequently tested for replication in an independent case-control study sample from the Ore-SUDS (n=688). The association analysis in the replication stage revealed 6 SNPs associated with SCD: CASQ2 region (rs17500488, P=0.04; rs3010396, P=0.007; rs7366407; P=0.04), NOS1AP (rs12084280, P=0.04; rs10918859, P=0.02), and 1 SNP located ≈26 kb upstream of GPD1L (rs9862154, P=0.04).
  
  
  CONCLUSIONS
  Common variations in or near CASQ2, GPD1L, and NOS1AP are associated with increased risk of SCD in patients with CAD. These findings provide further evidence for overlap between the genetic architecture of rare and common forms of SCD, and replication in additional populations is warranted.
authors.affiliation: The Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Shawn K
authors.initials: SK
authors.lastname: Westaway
authors.forename: Kyndaron
authors.initials: K
authors.lastname: Reinier
authors.forename: Adriana
authors.initials: A
authors.lastname: Huertas-Vazquez
authors.forename: Audrey
authors.initials: A
authors.lastname: Evanado
authors.forename: Carmen
authors.initials: C
authors.lastname: Teodorescu
authors.forename: Jo
authors.initials: J
authors.lastname: Navarro
authors.forename: Moritz F
authors.initials: MF
authors.lastname: Sinner
authors.forename: Karen
authors.initials: K
authors.lastname: Gunson
authors.forename: Jonathan
authors.initials: J
authors.lastname: Jui
authors.forename: Peter
authors.initials: P
authors.lastname: Spooner
authors.forename: Stefan
authors.initials: S
authors.lastname: Kaab
authors.forename: Sumeet S
authors.initials: SS
authors.lastname: Chugh
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D002155:Calsequestrin / Q000235:genetics*; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000473:pathology*; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D005993:Glycerolphosphate Dehydrogenase / Q000235:genetics*; D006801:Humans; D009922:Oregon; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C443109:CASQ2 protein, human; D002155:Calsequestrin; C488081:NOS1AP protein, human; C525035:GPD1L protein, human; D005993:Glycerolphosphate Dehydrogenase