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Genome-wide association study identifies GPC5 as a novel genetic locus protective against sudden cardiac arrest.
Tuesday,2012-11-06 12:19 America/Los_Angeles — eenright
| Title | Genome-wide association study identifies GPC5 as a novel genetic locus protective against sudden cardiac arrest. |
| Publication Type | Journal Article |
| Year of Publication | 2010 |
| Authors | Arking, DE, Reinier, K, Post, W, Jui, J, Hilton, G, O'Connor, A, Prineas, RJ, Boerwinkle, E, Psaty, BM, Tomaselli, GF, Rea, T, Sotoodehnia, N, Siscovick, DS, Burke, GL, Marbán, E, Spooner, PM, Chakravarti, A, Chugh, SS |
| Journal | PLoS One |
| Volume | 5 |
| Issue | 3 |
| Pagination | e9879 |
| Date Published | 2010 Mar 25 |
| ISSN | 1932-6203 |
| Keywords | Aged, Alleles, Case-Control Studies, Cohort Studies, Death, Sudden, Cardiac, Ethnic Groups, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Glypicans, Heart Diseases, Humans, Male, Middle Aged, Models, Genetic, Oligonucleotide Array Sequence Analysis, Oregon, Polymorphism, Single Nucleotide |
| Abstract | <p><b>BACKGROUND: </b>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.</p><p><b>METHODOLOGY/PRINCIPAL FINDINGS: </b>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).</p><p><b>CONCLUSIONS/SIGNIFICANCE: </b>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.</p> |
| DOI | 10.1371/journal.pone.0009879 |
| Alternate Journal | PLoS ONE |
| PubMed ID | 20360844 |
| PubMed Central ID | PMC2845611 |
| Grant List | N01HC55020 / HL / NHLBI NIH HHS / United States UL1RR025005 / RR / NCRR NIH HHS / United States N01 HC085086 / HC / NHLBI NIH HHS / United States N01HC55018 / HL / NHLBI NIH HHS / United States R01HL59367 / HL / NHLBI NIH HHS / United States UL1 RR025005 / RR / NCRR NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States R01 HL059367 / HL / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States N01-HC-55016 / HC / NHLBI NIH HHS / United States R01 HL088416 / HL / NHLBI NIH HHS / United States N01 HC055018 / HC / NHLBI NIH HHS / United States R01 HL086694 / HL / NHLBI NIH HHS / United States U01 HG004402 / HG / NHGRI NIH HHS / United States N01HC55022 / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC55015 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States R01 HL088456 / HL / NHLBI NIH HHS / United States U01HG004402 / HG / NHGRI NIH HHS / United States N01 HC055019 / HC / NHLBI NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States N01-HC-55019 / HC / NHLBI NIH HHS / United States R01HL087641 / HL / NHLBI NIH HHS / United States N01-HC-55015 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01-HC-55020 / HC / NHLBI NIH HHS / United States N01HC55016 / HL / NHLBI NIH HHS / United States N01HC55019 / HL / NHLBI NIH HHS / United States 1UL1RR025005 / RR / NCRR NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States U01HL080295 / HL / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01-HC-55018 / HC / NHLBI NIH HHS / United States N01HC55021 / HL / NHLBI NIH HHS / United States R01 HL087641 / HL / NHLBI NIH HHS / United States N01-HC-550 / HC / NHLBI NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States N01 HC055016 / HC / NHLBI NIH HHS / United States R01HL086694 / HL / NHLBI NIH HHS / United States |