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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
Date Issued
2019
Author(s)
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
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
DOI
10.1186/s12872-019-1002-x
Abstract
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.
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