Genetic QT score as a predictor of sudden cardiac death in participants with sleep-disordered breathing in the UK Biobank

Study Objectives: The goal of this study was to evaluate the association between a polygenic risk score (PRS) for QT prolongation (QTc-PRS), corrected QT intervals (QTc) and sudden cardiac death (SCD) in participants enrolled in the UK Biobank with and without sleep-disordered breathing (SDB). Methods: The QTc-PRS was calculated using allele copy number and previously reported effect estimates for each single nuclear polymorphism. Competing-risk regression models adjusting for age, sex, body mass index, QT prolonging medication, race, and comorbid cardiovascular conditions were used for SCD analyses. Results: A total of 500,584 participants were evaluated (56.5 ± 8 years, 54% female, 1.4% diagnosed with sleep apnea). A higher QTc-PRS was independently associated with the increased QTc interval duration (P < .0001). The mean QTc for the top QTc-PRS quintile was 15 msec longer than the bottom quintile (P < .001). SDB was found to be an effect modifier in the relationship between QTc-PRS and SCD. The adjusted hazard ratio per 5-unit change in QTc-PRS for SCD was 1.64 (95% confidence interval 1.16-2.31, P = .005) among those with SDB and 1.04 (95% confidence interval 0.95-1.14, P = .44) among those without SDB (P for interaction = .01). Black participants with SDB had significantly elevated adjusted risk of SCD (hazard ratio = 9.6, 95% confidence interval 1.24-74, P = .03). Conclusions: In the UK Biobank population, the QTc-PRS was associated with SCD among participants with SDB but not among those without SDB, indicating that SDB is a significant modifier of the genetic risk. Black participants with SDB had a particularly high risk of SCD.