title: Investigation of 95 variants identified in a genome-wide study for association with mortality after acute coronary syndrome.
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.
authors.affiliation: Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, USA. thomas.morgan@vanderbilt.edu
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Morgan
authors.forename: John A
authors.initials: JA
authors.lastname: House
authors.forename: Sharon
authors.initials: S
authors.lastname: Cresci
authors.forename: Philip
authors.initials: P
authors.lastname: Jones
authors.forename: Hooman
authors.initials: H
authors.lastname: Allayee
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Hazen
authors.forename: Yesha
authors.initials: Y
authors.lastname: Patel
authors.forename: Riyaz S
authors.initials: RS
authors.lastname: Patel
authors.forename: Danny J
authors.initials: DJ
authors.lastname: Eapen
authors.forename: Salina P
authors.initials: SP
authors.lastname: Waddy
authors.forename: Arshed A
authors.initials: AA
authors.lastname: Quyyumi
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Kleber
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.forename: Bernhard R
authors.initials: BR
authors.lastname: Winkelmann
authors.forename: Bernhard O
authors.initials: BO
authors.lastname: Boehm
authors.forename: Harlan M
authors.initials: HM
authors.lastname: Krumholz
authors.forename: John A
authors.initials: JA
authors.lastname: Spertus
mesh_terms: D054058:Acute Coronary Syndrome / Q000235:genetics* / Q000401:mortality; D000368:Aged; D000369:Aged, 80 and over; D000619:Aminohydrolases / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D005574:Formate-Tetrahydrofolate Ligase / Q000235:genetics; D014644:Genetic Variation; D055106:Genome-Wide Association Study / Q000706:statistics & numerical data*; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000235:genetics; D009203:Myocardial Infarction / Q000235:genetics / Q000401:mortality; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D009097:Multienzyme Complexes; C021836:formyl-methenyl-methylenetetrahydrofolate synthetase; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); D000619:Aminohydrolases; D005574:Formate-Tetrahydrofolate Ligase