{"doi":"10.1038/nature09753","title":"9p21 DNA variants associated with coronary artery disease impair interferon-γ signalling response","abstract":"Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in the 9p21 gene desert associated with coronary artery disease (CAD) and type 2 diabetes. Despite evidence for a role of the associated interval in neighbouring gene regulation, the biological underpinnings of these genetic associations with CAD or type 2 diabetes have not yet been explained. Here we identify 33 enhancers in 9p21; the interval is the second densest gene desert for predicted enhancers and six times denser than the whole genome (P < 6.55 × 10(-33)). The CAD risk alleles of SNPs rs10811656 and rs10757278 are located in one of these enhancers and disrupt a binding site for STAT1. Lymphoblastoid cell lines homozygous for the CAD risk haplotype show no binding of STAT1, and in lymphoblastoid cell lines homozygous for the CAD non-risk haplotype, binding of STAT1 inhibits CDKN2BAS (also known as CDKN2B-AS1) expression, which is reversed by short interfering RNA knockdown of STAT1. Using a new, open-ended approach to detect long-distance interactions, we find that in human vascular endothelial cells the enhancer interval containing the CAD locus physically interacts with the CDKN2A/B locus, the MTAP gene and an interval downstream of IFNA21. In human vascular endothelial cells, interferon-γ activation strongly affects the structure of the chromatin and the transcriptional regulation in the 9p21 locus, including STAT1-binding, long-range enhancer interactions and altered expression of neighbouring genes. Our findings establish a link between CAD genetic susceptibility and the response to inflammatory signalling in a vascular cell type and thus demonstrate the utility of genome-wide association study findings in directing studies to novel genomic loci and biological processes important for disease aetiology.","journal":"Nature","year":2011,"id":12036,"datarank":0.964941013910877,"base_score":6.432940092739179,"endowment":6.432940092739179,"self_citation_contribution":0.964941013910877,"citation_network_contribution":0.0,"self_endowment_contribution":0.964941013910877,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":621,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.059,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2011-02-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":95972,"name":"Dimple Notani","orcid":"0000-0002-9460-8070","position":1,"is_corresponding":false},{"id":95973,"name":"Xiaoyuan Song","orcid":"0000-0002-9011-5033","position":2,"is_corresponding":false},{"id":95974,"name":"Nazli G. Rahim","orcid":null,"position":3,"is_corresponding":false},{"id":95975,"name":"Bogdan Tanasa","orcid":null,"position":4,"is_corresponding":false},{"id":29403,"name":"Simona Volpi","orcid":"0000-0002-0353-2235","position":6,"is_corresponding":false},{"id":42981,"name":"Xiang-Dong Fu","orcid":null,"position":7,"is_corresponding":false},{"id":33022,"name":"Eric J. Topol","orcid":"0000-0002-1478-4729","position":8,"is_corresponding":false},{"id":73079,"name":"Michael G. Rosenfeld","orcid":"0000-0002-1572-156X","position":9,"is_corresponding":false},{"id":95977,"name":"Kelly A. Frazer","orcid":"0000-0002-6060-8902","position":10,"is_corresponding":false},{"id":95978,"name":"Bogdan Tanasă","orcid":"0000-0002-3797-8171","position":11,"is_corresponding":false},{"id":34205,"name":"Nathaniel D Heintzman","orcid":null,"position":12,"is_corresponding":false},{"id":43247,"name":"Xiang‐Dong Fu","orcid":"0000-0001-5499-8732","position":13,"is_corresponding":false},{"id":13530,"name":"Olivier Harismendy","orcid":"0000-0002-8098-9888","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","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":[]}