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The 9p21.3 Coronary Artery Disease Risk Locus Modulates Vascular Cell-State Transitions via Enhancer-Driven Regulation of MTAP.

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Title: The 9p21.3 Coronary Artery Disease Risk Locus Modulates Vascular Cell-State Transitions via Enhancer-Driven Regulation of MTAP.
Authors: Audam TN; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.; The Novo Nordisk Foundation Center for Genomic Mechanism of Disease at Broad Institute, Cambridge, MA, USA of MIT and Harvard.; These authors contributed equally., Schmandt B; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.; The Novo Nordisk Foundation Center for Genomic Mechanism of Disease at Broad Institute, Cambridge, MA, USA of MIT and Harvard.; These authors contributed equally., Huang Y; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.; The Novo Nordisk Foundation Center for Genomic Mechanism of Disease at Broad Institute, Cambridge, MA, USA of MIT and Harvard., Cho YB; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.; The Novo Nordisk Foundation Center for Genomic Mechanism of Disease at Broad Institute, Cambridge, MA, USA of MIT and Harvard., Murali M; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.; The Novo Nordisk Foundation Center for Genomic Mechanism of Disease at Broad Institute, Cambridge, MA, USA of MIT and Harvard., Kaalia R; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.; The Novo Nordisk Foundation Center for Genomic Mechanism of Disease at Broad Institute, Cambridge, MA, USA of MIT and Harvard., Agrawal S; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.; The Novo Nordisk Foundation Center for Genomic Mechanism of Disease at Broad Institute, Cambridge, MA, USA of MIT and Harvard., Liu J; Department of Cardiovascular Surgery, Zhongnan Hospital of Wuhan, Wuhan, China.; Hubei Provincial Engineering Research Center of Minimally Invasive Cardiovascular Surgery, Wuhan, China.; Wuhan Clinical Center for Minimally Invasive Treatment of Structural Heart Disease, Wuhan, China., Shi H; Department of Cardiovascular Surgery, Zhongnan Hospital of Wuhan, Wuhan, China.; Hubei Provincial Engineering Research Center of Minimally Invasive Cardiovascular Surgery, Wuhan, China.; Wuhan Clinical Center for Minimally Invasive Treatment of Structural Heart Disease, Wuhan, China., Zhou Y; Department of Cardiovascular Surgery, Zhongnan Hospital of Wuhan, Wuhan, China.; Hubei Provincial Engineering Research Center of Minimally Invasive Cardiovascular Surgery, Wuhan, China.; Wuhan Clinical Center for Minimally Invasive Treatment of Structural Heart Disease, Wuhan, China., Cao D; Department of Cardiovascular Surgery, Zhongnan Hospital of Wuhan, Wuhan, China.; Hubei Provincial Engineering Research Center of Minimally Invasive Cardiovascular Surgery, Wuhan, China.; Wuhan Clinical Center for Minimally Invasive Treatment of Structural Heart Disease, Wuhan, China., Jiang L; China National Center for Bioinformation, Beijing, China., Li Y; China National Center for Bioinformation, Beijing, China., Wen J; China National Center for Bioinformation, Beijing, China., Zhao H; China National Center for Bioinformation, Beijing, China., Saadat A; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA., Hall A; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA., Laber S; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA., Strobel S; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA., Chen S; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.; The Novo Nordisk Foundation Center for Genomic Mechanism of Disease at Broad Institute, Cambridge, MA, USA of MIT and Harvard.; The University of Chicago, Department of Human Genetics, Chicago, IL, USA., McGonagle E; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA., Stefek A; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA., Reeve MP; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland., Ham AM; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA., White CM; Department of Neuroscience, Scripps Research, La Jolla, CA, USA., Melanson M; Center for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Khera AV; Division of Cardiovascular Medicine, Bringham and Women's Hospital, Boston, MA, USA.; Verve Therapeutics, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA., Epstein CB; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA., Chaffin M; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA., Ellinor PT; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.; Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Wang M; China National Center for Bioinformation, Beijing, China.; College of Future Technology, Sino-Danish College, University of Chinese Academy of Sciences, Beijing, China., Daly MJ; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.; Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Karczewski KJ; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.; Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; The Novo Nordisk Foundation Center for Genomic Mechanism of Disease at Broad Institute, Cambridge, MA, USA of MIT and Harvard., Jones T; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.; The Novo Nordisk Foundation Center for Genomic Mechanism of Disease at Broad Institute, Cambridge, MA, USA of MIT and Harvard., Dashti H; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.; Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; The Novo Nordisk Foundation Center for Genomic Mechanism of Disease at Broad Institute, Cambridge, MA, USA of MIT and Harvard., Claussnitzer M; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.; Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; The Novo Nordisk Foundation Center for Genomic Mechanism of Disease at Broad Institute, Cambridge, MA, USA of MIT and Harvard.; Lead contact.
Source: BioRxiv : the preprint server for biology [bioRxiv] 2025 Nov 18. Date of Electronic Publication: 2025 Nov 18.
Publication Type: Journal Article; Preprint
Journal Info: Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
Database: MEDLINE Ultimate
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  Data: The 9p21.3 Coronary Artery Disease Risk Locus Modulates Vascular Cell-State Transitions via Enhancer-Driven Regulation of MTAP.
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  Data: <searchLink fieldCode="AU" term="%22Audam+TN%22">Audam TN</searchLink>; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.; The Novo Nordisk Foundation Center for Genomic Mechanism of Disease at Broad Institute, Cambridge, MA, USA of MIT and Harvard.; These authors contributed equally.<br /><searchLink fieldCode="AU" term="%22Schmandt+B%22">Schmandt B</searchLink>; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.; The Novo Nordisk Foundation Center for Genomic Mechanism of Disease at Broad Institute, Cambridge, MA, USA of MIT and Harvard.; These authors contributed equally.<br /><searchLink fieldCode="AU" term="%22Huang+Y%22">Huang Y</searchLink>; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.; 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China National Center for Bioinformation, Beijing, China.<br /><searchLink fieldCode="AU" term="%22Wen+J%22">Wen J</searchLink>; China National Center for Bioinformation, Beijing, China.<br /><searchLink fieldCode="AU" term="%22Zhao+H%22">Zhao H</searchLink>; China National Center for Bioinformation, Beijing, China.<br /><searchLink fieldCode="AU" term="%22Saadat+A%22">Saadat A</searchLink>; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.<br /><searchLink fieldCode="AU" term="%22Hall+A%22">Hall A</searchLink>; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.<br /><searchLink fieldCode="AU" term="%22Laber+S%22">Laber S</searchLink>; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.<br /><searchLink fieldCode="AU" term="%22Strobel+S%22">Strobel S</searchLink>; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.<br /><searchLink fieldCode="AU" term="%22Chen+S%22">Chen S</searchLink>; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.; The Novo Nordisk Foundation Center for Genomic Mechanism of Disease at Broad Institute, Cambridge, MA, USA of MIT and Harvard.; The University of Chicago, Department of Human Genetics, Chicago, IL, USA.<br /><searchLink fieldCode="AU" term="%22McGonagle+E%22">McGonagle E</searchLink>; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.<br /><searchLink fieldCode="AU" term="%22Stefek+A%22">Stefek A</searchLink>; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.<br /><searchLink fieldCode="AU" term="%22Reeve+MP%22">Reeve MP</searchLink>; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.<br /><searchLink fieldCode="AU" term="%22Ham+AM%22">Ham AM</searchLink>; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.<br /><searchLink fieldCode="AU" term="%22White+CM%22">White CM</searchLink>; Department of Neuroscience, Scripps Research, La Jolla, CA, USA.<br /><searchLink fieldCode="AU" term="%22Melanson+M%22">Melanson M</searchLink>; Center for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.<br /><searchLink fieldCode="AU" term="%22Khera+AV%22">Khera AV</searchLink>; Division of Cardiovascular Medicine, Bringham and Women's Hospital, Boston, MA, USA.; 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College of Future Technology, Sino-Danish College, University of Chinese Academy of Sciences, Beijing, China.<br /><searchLink fieldCode="AU" term="%22Daly+MJ%22">Daly MJ</searchLink>; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.; Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.<br /><searchLink fieldCode="AU" term="%22Karczewski+KJ%22">Karczewski KJ</searchLink>; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.; Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; The Novo Nordisk Foundation Center for Genomic Mechanism of Disease at Broad Institute, Cambridge, MA, USA of MIT and Harvard.<br /><searchLink fieldCode="AU" term="%22Jones+T%22">Jones T</searchLink>; Medical and Population Genetics Program, Cardiovascular Disease Initiative, & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.; 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