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Study Objectives: <p>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).</p> Methods: <p>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.</p> Results: <p>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 (<i>P</i> &lt; .0001). The mean QTc for the top QTc-PRS quintile was 15 msec longer than the bottom quintile (<i>P</i> &lt; .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, <i>P</i> = .005) among those with SDB and 1.04 (95% confidence interval 0.95–1.14, <i>P</i> = .44) among those without SDB (<i>P</i> for interaction = .01). Black participants with SDB had significantly elevated adjusted risk of SCD (hazard ratio = 9.6, 95% confidence interval 1.24–74, <i>P</i> = .03).</p> Conclusions: <p>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.</p> Citation: <p>Arora A, Zareba W, Woosley RL, et&#xa0;al. Genetic QT score as a predictor of sudden cardiac death in participants with sleep-disordered breathing in the UK Biobank. <i>J Clin Sleep Med</i>. 2025;21(3):549–557.</p>

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

  • 期刊论文

  • 发表日期：

    2025年3月1日

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  • Amit Arora,
  • Wojciech Zareba,
  • Raymond L. Woosley,
  • Yann C. Klimentidis,
  • Imran Y. Patel,
  • Stuart F. Quan,
  • Christopher Wendel,
  • Fadi Shamoun,
  • Stefano Guerra,
  • Sairam Parthasarathy,
  • Salma I. Patel

摘要

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.

Citation:

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. J Clin Sleep Med. 2025;21(3):549–557.