{"doi":"10.1101/2024.12.08.24318665","title":"Genetic Causes of Sudden Cardiac Arrest in the Community","abstract":"Abstract Background Annually 300,000 Americans experience sudden cardiac arrest (SCA). Studies in referral SCA cohorts have observed rare variants in genes associated with arrhythmia and cardiomyopathy. We sought to: (1) establish the population prevalence of rare disease-causing variants in a set of candidate genes and (2) confirm the association of disease-causing variants in these genes with SCA in two prospective population-based studies. Methods SCA patients (n=3264) were accrued from the Oregon Sudden Unexpected Death Study and the PREdiction of Sudden death in mulTi-ethnic cOmmunities (PRESTO) study and compared to control patients (n=13713) from the Atherosclerosis Risk in Communities (ARIC) study. Whole genome sequencing was performed. Disease-causing (likely pathogenic or pathogenic) variants in candidate genes associated with arrhythmia/cardiomyopathy were identified using updated American College of Medical Genetics and Genomics criteria. Gene- collapsing case-control analysis was performed using the conditional logistic regression-sequence kernel association test. Results We identified 300 disease-causing variants, the majority of which were in cardiomyopathy genes (71%). There were 136 patients (4.2%) in the SCA group and 351 patients (2.6%) in the control group with one or more disease-causing variants (OR 1.66, 95% confidence interval 1.33-2.07, p<0.001). We identified 13 genes associated with an increased risk of SCA, nine associated with cardiomyopathy ( BAG3, DSC2, DSG2, FLNC, LMNA, MYBPC3, TNNI3, TNNT2, TTN ) and four with arrhythmia ( CACNA1C, CASQ2, KCNH2, KCNQ1 ). Conclusions Disease-causing variants in cardiomyopathy genes were the predominant genetic cause of SCA. These findings inform which genes to include in genetic screening for SCA.","journal":"medRxiv","year":2024,"id":507246,"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":0.735,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1358859,"name":"Marco Mathias","orcid":null,"position":1,"is_corresponding":false},{"id":685235,"name":"Kotoka Nakamura","orcid":"0000-0001-5263-5006","position":2,"is_corresponding":false},{"id":21839,"name":"Jonathan P. Tyrer","orcid":"0000-0003-3724-4757","position":3,"is_corresponding":false},{"id":33596,"name":"Paul D.P. Pharoah","orcid":"0000-0001-8494-732X","position":4,"is_corresponding":false},{"id":685234,"name":"Harpriya Chugh","orcid":"0000-0002-6581-4246","position":5,"is_corresponding":false},{"id":488563,"name":"Kyndaron Reinier","orcid":"0000-0002-2588-6827","position":6,"is_corresponding":false},{"id":281964,"name":"Zeynep Coban‐Akdemir","orcid":"0000-0001-9928-9032","position":7,"is_corresponding":false},{"id":245381,"name":"Eric Boerwinkle","orcid":"0000-0001-8813-0544","position":8,"is_corresponding":false},{"id":588762,"name":"Bing Yu","orcid":"0000-0001-6013-5220","position":9,"is_corresponding":false},{"id":23013,"name":"Sumeet S. Chugh","orcid":"0000-0002-4417-5326","position":10,"is_corresponding":false},{"id":1010588,"name":"E. Kransdorf","orcid":"0000-0002-0507-2412","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T02:10:58.484528Z","pmid":"39936145","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":[]}