PLoS ONE (Mar 2010)

Genome-wide association study identifies GPC5 as a novel genetic locus protective against sudden cardiac arrest.

  • Dan E Arking,
  • Kyndaron Reinier,
  • Wendy Post,
  • Jonathan Jui,
  • Gina Hilton,
  • Ashley O'Connor,
  • Ronald J Prineas,
  • Eric Boerwinkle,
  • Bruce M Psaty,
  • Gordon F Tomaselli,
  • Thomas Rea,
  • Nona Sotoodehnia,
  • David S Siscovick,
  • Gregory L Burke,
  • Eduardo Marban,
  • Peter M Spooner,
  • Aravinda Chakravarti,
  • Sumeet S Chugh

DOI
https://doi.org/10.1371/journal.pone.0009879
Journal volume & issue
Vol. 5, no. 3
p. e9879

Abstract

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BackgroundExisting studies indicate a significant genetic component for sudden cardiac arrest (SCA) and genome-wide association studies (GWAS) provide an unbiased approach for identification of novel genes. We performed a GWAS to identify genetic determinants of SCA.Methodology/principal findingsWe used a case-control design within the ongoing Oregon Sudden Unexpected Death Study (Oregon-SUDS). Cases (n = 424) were SCAs with coronary artery disease (CAD) among residents of Portland, OR (2002-07, population approximately 1,000,000) and controls (n = 226) were residents with CAD, but no history of SCA. All subjects were of White-European ancestry and GWAS was performed using Affymetrix 500K/5.0 and 6.0 arrays. High signal markers were genotyped in SCA cases (n = 521) identified from the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS) (combined n = 19,611). No SNPs reached genome-wide significance (pConclusions/significanceA novel genetic locus for SCA, GPC5, was identified from Oregon-SUDS and successfully validated in the ARIC and CHS cohorts. Three other members of the Glypican family have been previously implicated in human disease, including cardiac conditions. The mechanism of this specific association requires further study.