Abstract 19869: Genome Wide Association Study of Perioperative Myocardial Infarction Following Coronary Bypass Grafting
The incidence of perioperative myocardial infarction (PMI) after cardiac surgery can be as high as 19%, and is associated with long-term mortality and morbidity. Identification of populations at risk for developing large infarcts or alternatively indicating presence of a cardioprotective state, as well as responsiveness to a protective agent remain high-priority knowledge gaps. We sought to identify novel common genetic variants associated with PMI in a genome-wide association study (GWAS) of patients undergoing CABG.
Methods: Using the Illumina 610quad chip, we conducted a GWAS for PMI in 1254 patients enrolled in the multicenter Genetics of Myocardial Adverse Outcomes and Graft Failure (GeneMagic) study, followed by a replication analysis in 644 patients from the Duke PEGASUS cohort. PMI was defined as CK-MB values ≥10xULN in the first two postoperative days, and was CEC adjudicated in the GeneMagic cohort. Sample and genotype QC analyses included assessing gender matching, autosome heterozygosity, cryptic relatedness, and population stratification, as well as filtering polymorphisms with minor allele frequencies <0.01 and departing from HWE.
Results: Following QC, 1193 patients in discovery cohort (100 cases/1093 controls), and 588 patients in replication cohort (108 cases/480 controls), all of European descent, were analyzed at 519,499 markers. In replicated analyses, we identified 14 SNPs associated with altered susceptibility to PMI (12 with increased risk [OR 1.35-2.44] and 2 with decreased risk [OR 0.4-0.73]), p<0.01 in both cohorts. The chromosomal distribution of association tests p-values in pooled analyses in presented in Fig A, and a quantile-quantile plot of observed vs expected p-values in Fig B.
Conclusion: Herein, we present a preliminary report of the first GWAS identifying multiple novel susceptibility loci for PMI. Further replication analyses in independent cohorts of cardiac surgical patients are ongoing.
- © 2012 by American Heart Association, Inc.