title: Genome-wide association of implantable cardioverter-defibrillator activation with life-threatening arrhythmias.
abstract: OBJECTIVE
  To identify genetic factors that would be predictive of individuals who require an implantable cardioverter-defibrillator (ICD), we conducted a genome-wide association study among individuals with an ICD who experienced a life-threatening arrhythmia (LTA; cases) vs. those who did not over at least a 3-year period (controls).
  
  
  BACKGROUND
  Most individuals that receive implantable cardioverter-defibrillators never experience a life-threatening arrhythmia. Genetic factors may help identify who is most at risk.
  
  
  METHODS
  Patients with an ICD and extended follow-up were recruited from 34 clinical sites with the goal of oversampling those who had experienced LTA, with a cumulative 607 cases and 297 controls included in the analysis. A total of 1,006 Caucasian patients were enrolled during a time period of 13 months. Arrhythmia status of 904 patients could be confirmed and their genomic data were included in the analysis. In this cohort, there were 704 males, 200 females, and the average age was 73.3 years. We genotyped DNA samples using the Illumina Human660 W Genotyping BeadChip and tested for association between genotype at common variants and the phenotype of having an LTA.
  
  
  CONCLUSIONS
  We did not find any associations reaching genome-wide significance, with the strongest association at chromosome 13, rs11856574 at P = 5×10⁻⁶. Loci previously implicated in phenotypes such as QT interval (measure of the time between the start of the Q wave and the end of the T wave as measured by electrocardiogram) were not found to be significantly associated with having an LTA. Although powered to detect such associations, we did not find common genetic variants of large effect associated with having a LTA in those of European descent. This indicates that common gene variants cannot be used at this time to guide ICD risk-stratification.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00664807.
authors.affiliation: Scripps Genomic Medicine, Scripps Translational Science Institute, La Jolla, California, United States of America.
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Murray
authors.forename: Erin N
authors.initials: EN
authors.lastname: Smith
authors.forename: Nikki
authors.initials: N
authors.lastname: Villarasa
authors.forename: Tara
authors.initials: T
authors.lastname: Nahey
authors.forename: Jeff
authors.initials: J
authors.lastname: Lande
authors.forename: Harold
authors.initials: H
authors.lastname: Goldberg
authors.forename: Marian
authors.initials: M
authors.lastname: Shaw
authors.forename: Lawrence
authors.initials: L
authors.lastname: Rosenthal
authors.forename: Brian
authors.initials: B
authors.lastname: Ramza
authors.forename: Jamshid
authors.initials: J
authors.lastname: Alaeddini
authors.forename: Xinqiang
authors.initials: X
authors.lastname: Han
authors.forename: Samir
authors.initials: S
authors.lastname: Damani
authors.forename: Orhan
authors.initials: O
authors.lastname: Soykan
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kowal
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Topol
mesh_terms: D000368:Aged; D001145:Arrhythmias, Cardiac / Q000235:genetics* / Q000401:mortality*; D016022:Case-Control Studies; D015331:Cohort Studies; D056915:DNA Copy Number Variations / Q000235:genetics*; D017147:Defibrillators, Implantable; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D015996:Survival Rate