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
BMC CARDIOVASCULAR DISORDERS
Authors: Westphal, Sabine; Stoppe, Christian; Gruenewald, Matthias; Bein, Berthold; Renner, Jochen; Cremer, Jochen; Coburn, Mark; Schaelte, Gereon; 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; Stevanovic, Ana; Rossaint, Rolf; Felzen, Marc; Goetzenich, Andreas; Moormann, Tobias; Chalk, Katharina; Knuefermann, Pascal; Boehm, Olaf; Hoeft, Andreas; Winterhalter, Michael; Iken, Sonja; Weber, Christian; Wiedenbeck, Carolin; Schwarzmann, Gerhard; Pense, Karin; Zierer, Andreas; Fichtlscherer, Stephan; Goerlach, Gerold; Wollbrueck, Matthias; Boening, Ursula; Weigand, Markus; Strauchmann, Julia; August, Konrad; Morsbach, Kai U.; Paxian, Markus; Reinhard, Konrad; Gruenewald, Matthias; Scholz, Jens; Broch, Ole; Francksen, Helga; Albrecht, Martin; Kuhr, Bernd; Heinze, Hermann; Paarmann, Hauke; Sievers, Hans-Hinrich; Klotz, Stefan; Hachenberg, Thomas; Werner, Christian; Mauff, Susanne; Alms, Angela; Bergt, Stefan; Roewer, Norbert
Abstract
BackgroundThe aim of our study was the identification of genetic variants associated with postoperative complications after cardiac surgery.MethodsWe 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.ResultsA 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=3.77x10(-8)) and 139 (adjusted for all other outcomes) SNPs showed promising association with p<1x10(-5) from the GWAS.ConclusionsWe 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 registrationThe study was registered with ClinicalTrials.gov NCT01067703, prospectively registered on 11 Feb 2010.