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
Westphal, Sabine ; Stoppe, Christian ; Gruenewald, Matthias ; Bein, Berthold ; Renner, Jochen ; Cremer, Jochen ; Coburn, Mark ; Schaelte, Gereon et al.
Boening, Andreas ; Niemann, Bernd ; Kletzin, Frank ; Roesner, Jan ; Strouhal, Ulrich ; Reyher, Christian ; Laufenberg-Feldmann, Rita ; Ferner, Marion ; Brandes, Ivo F ; Bauer, Martin ; Kortgen, Andreas ; Stehr, Sebastian N ; Wittmann, Maria ; Baumgarten, Georg ; Struck, Rafael ; Meyer-Treschan, Tanja ; Kienbaum, Peter ; Heringlake, Matthias ; Schoen, Julika ; Sander, Michael ; Treskatsch, Sascha ; Smul, Thorsten ; Wolwender, Ewa ; Schilling, Thomas ; Degenhardt, Frauke ; Franke, Andre ; Mucha, Soeren ; Tittmann, Lukas ; Kohlhaas, Madeline ; Fuernau, Georg ; Brosteanu, Oana ; Hasenclever, Dirk ; Zacharowski, Kai ; Meybohm, Patrick
Citable Link (URL):http://resolver.sub.uni-goettingen.de/purl?gs-1/15801
Abstract Background The aim of our study was the identification of genetic variants associated with postoperative complications after cardiac surgery. Methods 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. Results 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. Conclusions 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. Trial registration The study was registered with ClinicalTrials.gov NCT01067703, prospectively registered on 11 Feb 2010.