Genome-wide association study identifies GPC5 as a novel genetic locus protective against sudden cardiac arrest.
<h4>Background</h4>Existing 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.<h4>Me...
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oai:doaj.org-article:51ac1a05490642358c7c387f28fe040d2021-11-25T06:25:07ZGenome-wide association study identifies GPC5 as a novel genetic locus protective against sudden cardiac arrest.1932-620310.1371/journal.pone.0009879https://doaj.org/article/51ac1a05490642358c7c387f28fe040d2010-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20360844/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Existing 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.<h4>Methodology/principal findings</h4>We 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 (p<5x10(-8)). SNPs at 6 loci were prioritized for follow-up primarily based on significance of p<10(-4) and proximity to a known gene (CSMD2, GPR37L1, LIN9, B4GALNT3, GPC5, and ZNF592). The minor allele of GPC5 (GLYPICAN 5, rs3864180) was associated with a lower risk of SCA in Oregon-SUDS, an effect that was also observed in ARIC/CHS whites (p<0.05) and blacks (p<0.04). In a combined Cox proportional hazards model analysis that adjusted for race, the minor allele exhibited a hazard ratio of 0.85 (95% CI 0.74 to 0.98; p<0.01).<h4>Conclusions/significance</h4>A 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.Dan E ArkingKyndaron ReinierWendy PostJonathan JuiGina HiltonAshley O'ConnorRonald J PrineasEric BoerwinkleBruce M PsatyGordon F TomaselliThomas ReaNona SotoodehniaDavid S SiscovickGregory L BurkeEduardo MarbanPeter M SpoonerAravinda ChakravartiSumeet S ChughPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 3, p e9879 (2010) |
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Medicine R Science Q 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 Genome-wide association study identifies GPC5 as a novel genetic locus protective against sudden cardiac arrest. |
| description |
<h4>Background</h4>Existing 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.<h4>Methodology/principal findings</h4>We 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 (p<5x10(-8)). SNPs at 6 loci were prioritized for follow-up primarily based on significance of p<10(-4) and proximity to a known gene (CSMD2, GPR37L1, LIN9, B4GALNT3, GPC5, and ZNF592). The minor allele of GPC5 (GLYPICAN 5, rs3864180) was associated with a lower risk of SCA in Oregon-SUDS, an effect that was also observed in ARIC/CHS whites (p<0.05) and blacks (p<0.04). In a combined Cox proportional hazards model analysis that adjusted for race, the minor allele exhibited a hazard ratio of 0.85 (95% CI 0.74 to 0.98; p<0.01).<h4>Conclusions/significance</h4>A 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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Dan E Arking |
| title |
Genome-wide association study identifies GPC5 as a novel genetic locus protective against sudden cardiac arrest. |
| title_short |
Genome-wide association study identifies GPC5 as a novel genetic locus protective against sudden cardiac arrest. |
| title_full |
Genome-wide association study identifies GPC5 as a novel genetic locus protective against sudden cardiac arrest. |
| title_fullStr |
Genome-wide association study identifies GPC5 as a novel genetic locus protective against sudden cardiac arrest. |
| title_full_unstemmed |
Genome-wide association study identifies GPC5 as a novel genetic locus protective against sudden cardiac arrest. |
| title_sort |
genome-wide association study identifies gpc5 as a novel genetic locus protective against sudden cardiac arrest. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2010 |
| url |
https://doaj.org/article/51ac1a05490642358c7c387f28fe040d |
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