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Open Access 01-12-2011 | Research article

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

Authors: Thomas M Morgan, John A House, Sharon Cresci, Philip Jones, Hooman Allayee, Stanley L Hazen, Yesha Patel, Riyaz S Patel, Danny J Eapen, Salina P Waddy, Arshed A Quyyumi, Marcus E Kleber, Winfried März, Bernhard R Winkelmann, Bernhard O Boehm, Harlan M Krumholz, John A Spertus

Published in: BMC Medical Genetics | Issue 1/2011

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.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2350/12/127/prepub

Title: Investigation of 95 variants identified in a genome-wide study for association with mortality after acute coronary syndrome
Authors: Thomas M Morgan
John A House
Sharon Cresci
Philip Jones
Hooman Allayee
Stanley L Hazen
Yesha Patel
Riyaz S Patel
Danny J Eapen
Salina P Waddy
Arshed A Quyyumi
Marcus E Kleber
Winfried März
Bernhard R Winkelmann
Bernhard O Boehm
Harlan M Krumholz
John A Spertus
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2011
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/1471-2350-12-127

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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