Arora Amit, Zareba Wojciech, Woosley Raymond L, Klimentidis Yann C, Patel Imran Y, Quan Stuart F, Wendel Christopher, Shamoun Fadi, Guerra Stefano, Parthasarathy Sairam, Patel Salma I
Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona.
Division of Cardiology, University of Rochester Medical Center, Rochester, New York.
J Clin Sleep Med. 2025 Mar 1;21(3):549-557. doi: 10.5664/jcsm.11474.
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).
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.
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 ( < .0001). The mean QTc for the top QTc-PRS quintile was 15 msec longer than the bottom quintile ( < .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, = .005) among those with SDB and 1.04 (95% confidence interval 0.95-1.14, = .44) among those without SDB ( for interaction = .01). Black participants with SDB had significantly elevated adjusted risk of SCD (hazard ratio = 9.6, 95% confidence interval 1.24-74, = .03).
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.
Arora A, Zareba W, Woosley RL, et al. Genetic QT score as a predictor of sudden cardiac death in participants with sleep-disordered breathing in the UK Biobank. . 2025;21(3):549-557.
本研究的目的是评估英国生物银行中患有和未患有睡眠呼吸障碍（SDB）的参与者的QT间期延长多基因风险评分（QTc-PRS）、校正QT间期（QTc）与心源性猝死（SCD）之间的关联。
使用等位基因拷贝数和先前报道的每个单核苷酸多态性的效应估计值计算QTc-PRS。SCD分析采用竞争风险回归模型，并对年龄、性别、体重指数、延长QT的药物、种族和合并的心血管疾病进行校正。
共评估了500584名参与者（年龄56.5±8岁，54%为女性，1.4%被诊断为睡眠呼吸暂停）。较高的QTc-PRS与QTc间期持续时间增加独立相关（P<0.0001）。QTc-PRS最高五分位数的平均QTc比最低五分位数长15毫秒（P<0.001）。发现SDB是QTc-PRS与SCD之间关系的效应修饰因素。在患有SDB的参与者中，QTc-PRS每增加5个单位，SCD的校正风险比为1.64（95%置信区间1.16-2.31，P=0.005）；在未患有SDB的参与者中为1.04（95%置信区间0.95-1.14，P=0.44）（交互作用P=0.01）。患有SDB的黑人参与者的SCD校正风险显著升高（风险比=9.6，95%置信区间1.24-74，P=0.03）。
在英国生物银行人群中，QTc-PRS与患有SDB的参与者的SCD相关，但与未患有SDB的参与者无关，这表明SDB是遗传风险的重要修饰因素。患有SDB的黑人参与者的SCD风险特别高。
Arora A, Zareba W, Woosley RL,等。英国生物银行中睡眠呼吸障碍参与者的遗传QT评分作为心源性猝死的预测指标。《[期刊名称]》。2025；21(3):549-557。
