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 Cardiovasc Disord. 2019 Jan 24;19(1):26. doi: 10.1186/s12872-019-1002-x.

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.

Keywords: Acute kidney injury; Atrial fibrillation; Cardiac surgery; Delirium; Genome-wide association study; Myocardial infarction; Stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / diagnosis
  • Acute Kidney Injury / genetics*
  • Aged
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / genetics*
  • Cardiac Surgical Procedures / adverse effects*
  • Cytoskeletal Proteins / genetics
  • Delirium / diagnosis
  • Delirium / genetics*
  • Dual-Specificity Phosphatases / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • HSC70 Heat-Shock Proteins / genetics
  • Humans
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinase Phosphatases / genetics
  • Multicenter Studies as Topic
  • Myocardial Infarction / diagnosis
  • Myocardial Infarction / genetics*
  • Phosphoprotein Phosphatases / genetics
  • Polymorphism, Single Nucleotide*
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Ryanodine Receptor Calcium Release Channel / genetics
  • Stroke / diagnosis
  • Stroke / genetics*
  • Treatment Outcome

Substances

  • BBS9 protein, human
  • Cytoskeletal Proteins
  • HSC70 Heat-Shock Proteins
  • HSPA8 protein, human
  • RyR2 protein, human
  • Ryanodine Receptor Calcium Release Channel
  • Mitogen-Activated Protein Kinase Phosphatases
  • PHLPP2 protein, human
  • Phosphoprotein Phosphatases
  • DUSP4 protein, human
  • Dual-Specificity Phosphatases

Associated data

  • ClinicalTrials.gov/NCT01067703