| Title: | Genetic QT score as a predictor of sudden cardiac death in participants with sleep-disordered breathing in the UK Biobank. |
| Journal: | Journal of Clinical Sleep Medicine |
| Published: | 1 Mar 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39589075/ |
| DOI: | https://doi.org/10.5664/jcsm.11474 |
Publication 14355
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Abstract
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).</p>
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.</p>
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).</p>
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.</p>
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.</p>
12 Keywords
- Biological Specimen Banks
- Death, Sudden, Cardiac
- Electrocardiography
- Female
- Humans
- Long QT Syndrome
- Male
- Middle Aged
- Risk Factors
- Sleep Apnea Syndromes
- UK Biobank
- United Kingdom
11 Authors
- 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
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