{"doi":"10.1101/2023.11.07.23298237","title":"Genetic QT Score and Sleep Apnea as Predictors of Sudden Cardiac Death in the UK Biobank","abstract":"Introduction: 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. Methods: 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. Results: 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). Conclusion: 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.","journal":"medRxiv","year":2023,"id":413764,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9157,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":71412,"name":"Wojciech Zaręba","orcid":"0000-0003-4146-420X","position":1,"is_corresponding":false},{"id":825834,"name":"Raymond L. Woosley","orcid":"0000-0002-2588-328X","position":2,"is_corresponding":false},{"id":406718,"name":"Yann C. Klimentidis","orcid":"0000-0002-6065-4044","position":3,"is_corresponding":false},{"id":826137,"name":"Imran Patel","orcid":null,"position":4,"is_corresponding":false},{"id":300824,"name":"Stuart F. Quan","orcid":"0000-0002-9474-7679","position":5,"is_corresponding":false},{"id":341943,"name":"Christopher S. Wendel","orcid":"0000-0002-2383-5612","position":6,"is_corresponding":false},{"id":856372,"name":"Fadi Shamoun","orcid":"0000-0003-3890-7129","position":7,"is_corresponding":false},{"id":281741,"name":"Stefano Guerra","orcid":"0000-0001-7218-3246","position":8,"is_corresponding":false},{"id":231634,"name":"Sairam Parthasarathy","orcid":"0000-0002-1128-3005","position":9,"is_corresponding":false},{"id":460726,"name":"Salma Patel","orcid":"0000-0003-0900-043X","position":10,"is_corresponding":false},{"id":651886,"name":"Amit Arora","orcid":"0009-0001-8841-0316","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T01:22:01.321790Z","pmid":"37986981","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}