Objectives: To identify genetic factors that would be predictive of individuals who require an implantable cardioverterdefibrillator\n(ICD), we conducted a genome-wide association study among individuals with an ICD who experienced a lifethreatening\narrhythmia (LTA; cases) vs. those who did not over at least a 3-year period (controls).\nBackground: Most individuals that receive implantable cardioverter-defibrillators never experience a life-threatening\narrhythmia. Genetic factors may help identify who is most at risk.\nMethods: Patients with an ICD and extended follow-up were recruited from 34 clinical sites with the goal of oversampling\nthose who had experienced LTA, with a cumulative 607 cases and 297 controls included in the analysis. A total of 1,006\nCaucasian patients were enrolled during a time period of 13 months. Arrhythmia status of 904 patients could be confirmed\nand their genomic data were included in the analysis. In this cohort, there were 704 males, 200 females, and the average age\nwas 73.3 years. We genotyped DNA samples using the Illumina Human660 W Genotyping BeadChip and tested for\nassociation between genotype at common variants and the phenotype of having an LTA.\nResults and Conclusions: We did not find any associations reaching genome-wide significance, with the strongest\nassociation at chromosome 13, rs11856574 at P = 561026. Loci previously implicated in phenotypes such as QT interval\n(measure of the time between the start of the Q wave and the end of the T wave as measured by electrocardiogram) were\nnot found to be significantly associated with having an LTA. Although powered to detect such associations, we did not find\ncommon genetic variants of large effect associated with having a LTA in those of European descent. This indicates that\ncommon gene variants cannot be used at this time to guide ICD risk-stratification.
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