title: Genome-wide association study in takotsubo syndrome - Preliminary results and future directions.
abstract: BACKGROUND
  Takotsubo syndrome (TS) is an acute non-ischemic cardiomyopathy characterized by transient regional systolic dysfunction of the left and/or right ventricle with still unknown etiology. The aim of the current study was to conduct for the first time a genome-wide association study (GWAS) in a cohort of TS patients to identify potential genetic risk variants.
  
  
  METHODS
  This single-center study was conducted at the University Heart Center Lübeck from 2008 to 2016. DNA isolation was done according to standard protocols. Imputation of genotypes were performed at the Michigan Imputation Server (https://imputationserver.sph.umich.edu) using the 1000G Phase 3 v5 reference panel.
  
  
  RESULTS
  The study population consisted of 96 TS patients (91 females, 5 males) with a mean age of 71.9±10.4years and 475 healthy controls (268 males, 207 females). The results of GWAS analysis showed several promising candidate loci (68 loci after applying threshold of p<5∗10-4and MAF>5%). Of these 68 loci, 18 loci contained top single nucleotide polymorphisms (SNPs) that were supported by SNPs in high Linkage Disequilibrium (r2>0.8) with p<10-3. Two out of the 18 loci contained SNP with hits in the GWAS catalog (traits: blood pressure, thyroid stimulating hormone).
  
  
  CONCLUSIONS
  This first GWAS analysis in a larger cohort of patients with TS showed promising preliminary results. Further intensive research efforts of international collaborators are now necessary to enable deep-phenotyping of TS patients to ultimately assess a potential genetic cause of TS.
authors.affiliation: University Heart Center of Lübeck, Medical Clinic II, Department of Cardiology, Angiology, Intensive Care Medicine, Lübeck, Germany; German Center for Cardiovascular Research (DZHK), partner site Hamburg/Kiel/Lübeck, Lübeck, Germany. Electronic address: ingoeitel@gmx.de.
authors.forename: Ingo
authors.initials: I
authors.lastname: Eitel
authors.affiliation: University Heart Center of Lübeck, Medical Clinic II, Department of Cardiology, Angiology, Intensive Care Medicine, Lübeck, Germany; German Center for Cardiovascular Research (DZHK), partner site Hamburg/Kiel/Lübeck, Lübeck, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Moeller
authors.affiliation: German Center for Cardiovascular Research (DZHK), partner site Hamburg/Kiel/Lübeck, Lübeck, Germany; Institute for Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany; Department of Periodontology and Synoptic Dentistry, Institute for Dental and Craniofacial Sciences, Charité - University Medicine Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Munz
authors.affiliation: University Heart Center of Lübeck, Medical Clinic II, Department of Cardiology, Angiology, Intensive Care Medicine, Lübeck, Germany; German Center for Cardiovascular Research (DZHK), partner site Hamburg/Kiel/Lübeck, Lübeck, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Stiermaier
authors.affiliation: Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.affiliation: University Heart Center of Lübeck, Medical Clinic II, Department of Cardiology, Angiology, Intensive Care Medicine, Lübeck, Germany; German Center for Cardiovascular Research (DZHK), partner site Hamburg/Kiel/Lübeck, Lübeck, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Thiele
authors.affiliation: University Heart Center of Lübeck, Medical Clinic II, Department of Cardiology, Angiology, Intensive Care Medicine, Lübeck, Germany; German Center for Cardiovascular Research (DZHK), partner site Hamburg/Kiel/Lübeck, Lübeck, Germany; Institute for Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Erdmann
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D005544:Forecasting; D055106:Genome-Wide Association Study / Q000379:methods* / Q000639:trends; D006801:Humans; D008297:Male; D008875:Middle Aged; D054549:Takotsubo Cardiomyopathy / Q000175:diagnosis* / Q000235:genetics*
keywords: GWAS; Genetics; Pathophysiology; Stress cardiomyopathy; Takotsubo syndrome