Investigation of 95 variants identified in a genome-wide study for association with mortality after acute coronary syndrome

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Investigation of 95 variants identified in a genome-wide study for association with mortality after acute coronary syndrome

Please use this identifier to cite or link to this item: http://dx.doi.org/10.1186/1471-2350-12-127

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dc.contributor.author Morgan, Thomas M.
dc.contributor.author House, John A.
dc.contributor.author Cresci, Sharon
dc.contributor.author Jones, Philip
dc.contributor.author Allayee, Hooman
dc.contributor.author Hazen, Stanley L.
dc.contributor.author Patel, Yesha
dc.contributor.author Patel, Riyaz S.
dc.contributor.author Eapen, Danny J.
dc.contributor.author Waddy, Salina P.
dc.contributor.author Quyyumi, Arshed A.
dc.contributor.author Kleber, Marcus E.
dc.contributor.author März, Winfried
dc.contributor.author Winkelmann, Bernhard R.
dc.contributor.author Boehm, Bernhard O.
dc.contributor.author Krumholz, Harlan M.
dc.contributor.author Spertus, John A.
dc.date.accessioned 2012-08-30T05:24:37Z
dc.date.available 2012-08-30T05:24:37Z
dc.date.issued 2011-09-29
dc.identifier.citation BMC Medical Genetics. 2011 Sep 29;12(1):127
dc.identifier.uri http://dx.doi.org/10.1186/1471-2350-12-127
dc.identifier.uri http://hdl.handle.net/10355/15097
dc.description.abstract Abstract Background Genome-wide association studies (GWAS) have identified new candidate genes for the occurrence of acute coronary syndrome (ACS), but possible effects of such genes on survival following ACS have yet to be investigated. Methods We examined 95 polymorphisms in 69 distinct gene regions identified in a GWAS for premature myocardial infarction for their association with post-ACS mortality among 811 whites recruited from university-affiliated hospitals in Kansas City, Missouri. We then sought replication of a positive genetic association in a large, racially diverse cohort of myocardial infarction patients (N = 2284) using Kaplan-Meier survival analyses and Cox regression to adjust for relevant covariates. Finally, we investigated the apparent association further in 6086 additional coronary artery disease patients. Results After Cox adjustment for other ACS risk factors, of 95 SNPs tested in 811 whites only the association with the rs6922269 in MTHFD1L was statistically significant, with a 2.6-fold mortality hazard (P = 0.007). The recessive A/A genotype was of borderline significance in an age- and race-adjusted analysis of the entire combined cohort (N = 3095; P = 0.052), but this finding was not confirmed in independent cohorts (N = 6086). Conclusions We found no support for the hypothesis that the GWAS-identified variants in this study substantially alter the probability of post-ACS survival. Large-scale, collaborative, genome-wide studies may be required in order to detect genetic variants that are robustly associated with survival in patients with coronary artery disease.
dc.title Investigation of 95 variants identified in a genome-wide study for association with mortality after acute coronary syndrome
dc.type Journal Article
dc.date.updated 2012-08-30T05:24:37Z
dc.description.version Peer Reviewed
dc.language.rfc3066 en
dc.rights.holder Thomas M Morgan et al.; licensee BioMed Central Ltd.


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