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
medRxiv. 2023 Nov 8:2023.11.07.23298237. doi: 10.1101/2023.11.07.23298237.
The goal of this study was to evaluate the association between a polygenic risk score (PRS) for QT prolongation (QTc-PRS), QTc intervals and mortality in patients enrolled in the UK Biobank with and without sleep apnea.
The QTc-PRS was calculated using allele copy number and previously reported effect estimates for each single nuclear polymorphism SNP. Competing-risk regression models adjusting for age, sex, BMI, QT prolonging medication, race, and comorbid cardiovascular conditions were used for sudden cardiac death (SCD) analyses.
500,584 participants were evaluated (56.5 ±8 years, 54% women, 1.4% diagnosed with sleep apnea). A higher QTc-PRS was independently associated with the increased QTc interval duration (p<0.0001). The mean QTc for the top QTc-PRS quintile was 15 msec longer than the bottom quintile (p<0.001). Sleep apnea was found to be an effect modifier in the relationship between QTc-PRS and SCD. The adjusted HR per 5-unit change in QTc-PRS for SCD was 1.64 (95% CI 1.16 - 2.31, p=0.005) among those with sleep apnea and 1.04 (95% CI 0.95 - 1.14, p=0.44) among those without sleep apnea (p for interaction =0.01). Black participants with sleep apnea had significantly elevated adjusted risk of SCD compared to White participants (HR=9.6, 95% CI 1.24 - 74, p=0.03).
In the UK Biobank population, the QTc-PRS was associated with SCD among participants with sleep apnea but not among those without sleep apnea, indicating that sleep apnea is a significant modifier of the genetic risk. Black participants with sleep apnea had a particularly high risk of SCD.
本研究的目的是评估英国生物银行中伴有和不伴有睡眠呼吸暂停的患者的QT间期延长多基因风险评分（QTc-PRS）、QTc间期与死亡率之间的关联。
使用等位基因拷贝数和先前报道的每个单核苷酸多态性（SNP）的效应估计值来计算QTc-PRS。采用竞争风险回归模型对年龄、性别、体重指数、延长QT间期的药物、种族和合并的心血管疾病进行校正，以分析心源性猝死（SCD）。
共评估了500,584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）。发现睡眠呼吸暂停是QTc-PRS与SCD之间关系的效应修饰因素。伴有睡眠呼吸暂停者中，QTc-PRS每增加5个单位，SCD的校正风险比（HR）为1.64（95%可信区间1.16 - 2.31，p=0.005）；不伴有睡眠呼吸暂停者中，HR为1.04（95%可信区间0.95 - 1.14，p=0.44）（交互作用p=0.01）。与白人参与者相比，伴有睡眠呼吸暂停的黑人参与者SCD的校正风险显著升高（HR=9.6，95%可信区间1.24 - 74，p=0.03）。
在英国生物银行人群中，QTc-PRS与伴有睡眠呼吸暂停的参与者的SCD相关，但与不伴有睡眠呼吸暂停的参与者无关，这表明睡眠呼吸暂停是遗传风险的重要修饰因素。伴有睡眠呼吸暂停的黑人参与者SCD风险特别高。
