Genome-wide association study of myocardial infarction, atrial fibrillation, acute stroke, acute kidney injury and delirium after cardiac surgery – a sub-analysis of the RIPHeart-Study

The aim of our study was the identification of genetic variants associated with postoperative complications after cardiac surgery. We conducted a prospective, double-blind, multicenter, randomized trial (RIPHeart). We performed a genome-wide association study (GWAS) in 1170 patients of both genders (871 males, 299 females) from the RIPHeart-Study cohort. Patients undergoing non-emergent cardiac surgery were included. Primary endpoint comprises a binary composite complication rate covering atrial fibrillation, delirium, non-fatal myocardial infarction, acute renal failure and/or any new stroke until hospital discharge with a maximum of fourteen days after surgery. A total of 547,644 genotyped markers were available for analysis. Following quality control and adjustment for clinical covariate, one SNP reached genome-wide significance ( PHLPP2 , rs78064607, p = 3.77 × 10 − 8 ) and 139 (adjusted for all other outcomes) SNPs showed promising association with p < 1 × 10 − 5 from the GWAS. We identified several potential loci, in particular PHLPP2 , BBS9 , RyR2 , DUSP4 and HSPA8 , associated with new-onset of atrial fibrillation, delirium, myocardial infarction, acute kidney injury and stroke after cardiac surgery. The study was registered with ClinicalTrials.gov NCT01067703, prospectively registered on 11 Feb 2010.