{"doi":"10.1101/2023.07.01.547335","title":"Functional Genomics in Human iPSC-Derived Sinoatrial Node Cells Reveals Shared Regulatory Determinants of Heart Rate and Atrial Fibrillation","abstract":"ABSTRACT Human model systems for functional genomics of heart rhythm are needed to translate genome wide association studies into biological insight and actionable targets. Here we develop a human induced pluripotent stem cell sinoatrial node system that recapitulated the transcriptional and epigenetic heterogeneity of primary human pacemaker tissue, permitting exploration of heart rhythm-associated single nucleotide polymorphisms (SNPs) in a cell subtype-specific manner. Using self-transcribing active regulatory region sequencing (STARR-seq), we experimentally validated numerous enhancers containing heart rhythm associated variants. We demonstrated the utility of this platform for fine mapping of candidate causal SNPs by identifying an AF-associated variant at the ATXN1 locus that affects signal responsiveness of an enhancer, and a variant at the GNB4 locus that regulates cardiac autonomic sensitivity, leading to a pleiotropic effect on heart rate and atrial fibrillation. Taken together, these data establish a robust human cellular system to explore the mechanistic basis of heart rhythm heritability.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":392467,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.871,"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":510426,"name":"Xianglong Zhang","orcid":"0000-0003-0977-5673","position":1,"is_corresponding":false},{"id":664192,"name":"Daniel Lu","orcid":null,"position":2,"is_corresponding":false},{"id":347834,"name":"Olaia F. Vila","orcid":"0000-0002-1238-2275","position":3,"is_corresponding":false},{"id":1025961,"name":"Vanessa Arias","orcid":"0000-0002-0748-5894","position":4,"is_corresponding":false},{"id":563926,"name":"Jasper Lee","orcid":null,"position":5,"is_corresponding":false},{"id":316852,"name":"Vasanth Vedantham","orcid":"0000-0003-1032-700X","position":10,"is_corresponding":false},{"id":285200,"name":"Yi‐Hsiang Hsu","orcid":"0000-0003-3350-5390","position":11,"is_corresponding":false},{"id":985016,"name":"Chi-Ming Li","orcid":null,"position":12,"is_corresponding":false},{"id":74035,"name":"Gabriel B. Loeb","orcid":"0000-0002-8514-8180","position":13,"is_corresponding":false},{"id":328003,"name":"Arun Padmanabhan","orcid":"0000-0002-6806-3046","position":14,"is_corresponding":false},{"id":316847,"name":"Roland S. Wu","orcid":"0000-0002-8253-1192","position":15,"is_corresponding":false},{"id":1166532,"name":"Yen-Sin Ang","orcid":null,"position":16,"is_corresponding":false},{"id":713227,"name":"J Engel","orcid":"0000-0002-7512-8127","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T01:18:56.730121Z","pmid":"37425707","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":[]}