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
Sabine Westphal, Christian Stoppe, Matthias Gruenewald, Berthold Bein, Jochen Renner, Jochen Cremer, Mark Coburn, Gereon Schaelte, Andreas Boening, Bernd Niemann, Frank Kletzin, Jan Roesner, Ulrich Strouhal, Christian Reyher, Rita Laufenberg-Feldmann, Marion Ferner, Ivo Brandes, Martin Bauer, Andreas Kortgen, Sebastian Stehr, Maria Wittmann, Georg Baumgarten, Rafael Struck, Tanja Meyer-Treschan, Peter Kienbaum, Matthias Heringlake, Julika Schoen, Michael Sander, Sascha Treskatsch, Thorsten Smul, Ewa Wolwender, Thomas Schilling, Frauke Degenhardt, Andre Franke, Soeren Mucha, Lukas Tittmann, Madeline Kohlhaas, Georg Fuernau, Oana Brosteanu, Dirk Hasenclever, Kai Zacharowski, Patrick Meybohm
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 x 10(- 8)) and 139 (adjusted for all other outcomes) SNPs showed promising association with p < 1 x 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.