{"doi":"10.1101/2021.06.07.447388","title":"Cell-specific chromatin landscape of human coronary artery resolves regulatory mechanisms of disease risk","abstract":"Abstract Coronary artery disease (CAD) is a complex inflammatory disease involving genetic influences across several cell types. Genome-wide association studies (GWAS) have identified over 170 loci associated with CAD, where the majority of risk variants reside in noncoding DNA sequences impacting cis -regulatory elements (CREs). Here, we applied single-cell ATAC-seq to profile 28,316 cells across coronary artery segments from 41 patients with varying stages of CAD, which revealed 14 distinct cellular clusters. We mapped ~320,000 accessible sites across all cells, identified cell type-specific elements, transcription factors, and prioritized functional CAD risk variants via quantitative trait locus and sequence-based predictive modeling. We identified a number of candidate mechanisms for smooth muscle cell transition states and identified putative binding sites for risk variants. We further employed CRE to gene linkage to nominate disease-associated key driver transcription factors such as PRDM16 and TBX2. This single cell atlas provides a critical step towards interpreting cis -regulatory mechanisms in the vessel wall across the continuum of CAD risk.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":216644,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.852,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":23419,"name":"Shengen Shawn Hu","orcid":"0000-0002-9691-7344","position":1,"is_corresponding":false},{"id":558981,"name":"José Verdezoto Mosquera","orcid":"0000-0002-2816-2250","position":2,"is_corresponding":false},{"id":558977,"name":"Wei Feng","orcid":"0000-0002-2177-1387","position":3,"is_corresponding":false},{"id":441470,"name":"Chani J. Hodonsky","orcid":"0000-0001-8566-5877","position":4,"is_corresponding":false},{"id":558978,"name":"Doris Wong","orcid":"0000-0002-1094-8677","position":5,"is_corresponding":false},{"id":298086,"name":"Gaëlle Auguste","orcid":"0000-0003-4900-6959","position":6,"is_corresponding":false},{"id":85490,"name":"Katia Sol‐Church","orcid":null,"position":7,"is_corresponding":false},{"id":515104,"name":"Emily Farber","orcid":"0000-0003-3474-2304","position":8,"is_corresponding":false},{"id":474991,"name":"Soumya Kundu","orcid":"0000-0003-2425-3902","position":9,"is_corresponding":false},{"id":360,"name":"Anshul Kundaje","orcid":"0000-0003-3084-2287","position":10,"is_corresponding":false},{"id":812552,"name":"Nicolás López","orcid":"0000-0003-0659-4500","position":11,"is_corresponding":false},{"id":236715,"name":"Lijiang Ma","orcid":"0000-0001-6498-5556","position":12,"is_corresponding":false},{"id":599968,"name":"Saikat Ghosh","orcid":"0000-0002-5171-368X","position":13,"is_corresponding":false},{"id":428049,"name":"Suna Önengüt-Gümüşcü","orcid":"0000-0002-6563-8334","position":14,"is_corresponding":false},{"id":3451,"name":"Euan A. Ashley","orcid":"0000-0001-9418-9577","position":15,"is_corresponding":false},{"id":21976,"name":"Thomas Quertermous","orcid":"0000-0002-7645-9067","position":16,"is_corresponding":false},{"id":235795,"name":"Aloke V. Finn","orcid":"0000-0003-0359-0184","position":17,"is_corresponding":false},{"id":236255,"name":"Nicholas J. Leeper","orcid":"0000-0002-0905-2806","position":18,"is_corresponding":false},{"id":245353,"name":"Jason C. Kovacic","orcid":"0000-0003-4555-769X","position":19,"is_corresponding":false},{"id":812949,"name":"Johan L.M. Björkgren","orcid":null,"position":20,"is_corresponding":false},{"id":43221,"name":"Chongzhi Zang","orcid":"0000-0003-4812-3627","position":21,"is_corresponding":false},{"id":236712,"name":"Clint L. Miller","orcid":"0000-0003-4276-3607","position":22,"is_corresponding":false},{"id":236711,"name":"Adam W. Turner","orcid":"0000-0002-3087-9939","position":0,"is_corresponding":true}],"reference_count":117,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:53:11.245932Z","pmid":null,"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":[]}