Skip to main content

Genome-wide association study of perioperative myocardial infarction after coronary artery bypass surgery.

Publication ,  Journal Article
Kertai, MD; Li, Y-J; Li, Y-W; Ji, Y; Alexander, J; Newman, MF; Smith, PK; Joseph, D; Mathew, JP; Podgoreanu, MV ...
Published in: BMJ Open
May 6, 2015

OBJECTIVES: Identification of patient subpopulations susceptible to develop myocardial infarction (MI) or, conversely, those displaying either intrinsic cardioprotective phenotypes or highly responsive to protective interventions remain high-priority knowledge gaps. We sought to identify novel common genetic variants associated with perioperative MI in patients undergoing coronary artery bypass grafting using genome-wide association methodology. SETTING: 107 secondary and tertiary cardiac surgery centres across the USA. PARTICIPANTS: We conducted a stage I genome-wide association study (GWAS) in 1433 ethnically diverse patients of both genders (112 cases/1321 controls) from the Genetics of Myocardial Adverse Outcomes and Graft Failure (GeneMAGIC) study, and a stage II analysis in an expanded population of 2055 patients (225 cases/1830 controls) combined from the GeneMAGIC and Duke Perioperative Genetics and Safety Outcomes (PEGASUS) studies. Patients undergoing primary non-emergent coronary bypass grafting were included. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome variable was perioperative MI, defined as creatine kinase MB isoenzyme (CK-MB) values ≥10× upper limit of normal during the first postoperative day, and not attributable to preoperative MI. Secondary outcomes included postoperative CK-MB as a quantitative trait, or a dichotomised phenotype based on extreme quartiles of the CK-MB distribution. RESULTS: Following quality control and adjustment for clinical covariates, we identified 521 single nucleotide polymorphisms in the stage I GWAS analysis. Among these, 8 common variants in 3 genes or intergenic regions met p<10(-5) in stage II. A secondary analysis using CK-MB as a quantitative trait (minimum p=1.26×10(-3) for rs609418), or a dichotomised phenotype based on extreme CK-MB values (minimum p=7.72×10(-6) for rs4834703) supported these findings. Pathway analysis revealed that genes harbouring top-scoring variants cluster in pathways of biological relevance to extracellular matrix remodelling, endoplasmic reticulum-to-Golgi transport and inflammation. CONCLUSIONS: Using a two-stage GWAS and pathway analysis, we identified and prioritised several potential susceptibility loci for perioperative MI.

Duke Scholars

Published In

BMJ Open

DOI

EISSN

2044-6055

Publication Date

May 6, 2015

Volume

5

Issue

5

Start / End Page

e006920

Location

England

Related Subject Headings

  • Prognosis
  • Myocardium
  • Myocardial Infarction
  • Monitoring, Physiologic
  • Middle Aged
  • Male
  • Intraoperative Complications
  • Humans
  • Genome-Wide Association Study
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kertai, M. D., Li, Y.-J., Li, Y.-W., Ji, Y., Alexander, J., Newman, M. F., … Duke Perioperative Genetics and Safety Outcomes (PEGASUS) Investigative Team, . (2015). Genome-wide association study of perioperative myocardial infarction after coronary artery bypass surgery. BMJ Open, 5(5), e006920. https://doi.org/10.1136/bmjopen-2014-006920
Kertai, Miklos D., Yi-Ju Li, Yen-Wei Li, Yunqi Ji, John Alexander, Mark F. Newman, Peter K. Smith, et al. “Genome-wide association study of perioperative myocardial infarction after coronary artery bypass surgery.BMJ Open 5, no. 5 (May 6, 2015): e006920. https://doi.org/10.1136/bmjopen-2014-006920.
Kertai MD, Li Y-J, Li Y-W, Ji Y, Alexander J, Newman MF, et al. Genome-wide association study of perioperative myocardial infarction after coronary artery bypass surgery. BMJ Open. 2015 May 6;5(5):e006920.
Kertai, Miklos D., et al. “Genome-wide association study of perioperative myocardial infarction after coronary artery bypass surgery.BMJ Open, vol. 5, no. 5, May 2015, p. e006920. Pubmed, doi:10.1136/bmjopen-2014-006920.
Kertai MD, Li Y-J, Li Y-W, Ji Y, Alexander J, Newman MF, Smith PK, Joseph D, Mathew JP, Podgoreanu MV, Duke Perioperative Genetics and Safety Outcomes (PEGASUS) Investigative Team. Genome-wide association study of perioperative myocardial infarction after coronary artery bypass surgery. BMJ Open. 2015 May 6;5(5):e006920.

Published In

BMJ Open

DOI

EISSN

2044-6055

Publication Date

May 6, 2015

Volume

5

Issue

5

Start / End Page

e006920

Location

England

Related Subject Headings

  • Prognosis
  • Myocardium
  • Myocardial Infarction
  • Monitoring, Physiologic
  • Middle Aged
  • Male
  • Intraoperative Complications
  • Humans
  • Genome-Wide Association Study
  • Female