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.
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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, RIPHeart-Study Collaborators
Аннотация
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.