1 line
No EOL
40 KiB
Text
1 line
No EOL
40 KiB
Text
{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,1,21]],"date-time":"2024-01-21T16:55:39Z","timestamp":1705856139728},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T00:00:00Z","timestamp":1655769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["TRR259","SFB958","SE2016\/13-1","SE2016\/17-1","NO246\/17-1","KR3985\/12-1","EXC 2167-390884018","INST 336\/104-1","INST 336\/114-1"]},{"name":"Leicester NIHR Leicester Biomedical Research Centre"},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"crossref"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n <jats:sec>\n <jats:title>Aims<\/jats:title>\n <jats:p>The present study aims to characterize the genetic risk architecture of bicuspid aortic valve (BAV) disease, the most common congenital heart defect.<\/jats:p>\n <\/jats:sec>\n <jats:sec>\n <jats:title>Methods and results<\/jats:title>\n <jats:p>We carried out a genome-wide association study (GWAS) including 2236 BAV patients and 11 604 controls. This led to the identification of a new risk locus for BAV on chromosome 3q29. The single nucleotide polymorphism rs2550262 was genome-wide significant BAV associated (P = 3.49 \u00d7 10\u221208) and was replicated in an independent case\u2013control sample. The risk locus encodes a deleterious missense variant in MUC4 (p.Ala4821Ser), a gene that is involved in epithelial-to-mesenchymal transformation. Mechanistical studies in zebrafish revealed that loss of Muc4 led to a delay in cardiac valvular development suggesting that loss of MUC4 may also play a role in aortic valve malformation. The GWAS also confirmed previously reported BAV risk loci at PALMD (P = 3.97 \u00d7 10\u221216), GATA4 (P = 1.61 \u00d7 10\u221209), and TEX41 (P = 7.68 \u00d7 10\u221204). In addition, the genetic BAV architecture was examined beyond the single-marker level revealing that a substantial fraction of BAV heritability is polygenic and \u223c20% of the observed heritability can be explained by our GWAS data. Furthermore, we used the largest human single-cell atlas for foetal gene expression and show that the transcriptome profile in endothelial cells is a major source contributing to BAV pathology.<\/jats:p>\n <\/jats:sec>\n <jats:sec>\n <jats:title>Conclusion<\/jats:title>\n <jats:p>Our study provides a deeper understanding of the genetic risk architecture of BAV formation on the single marker and polygenic level.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/cvr\/cvac099","type":"journal-article","created":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T18:36:55Z","timestamp":1655836615000},"page":"857-866","source":"Crossref","is-referenced-by-count":6,"title":["Elucidation of the genetic causes of bicuspid aortic valve disease"],"prefix":"10.1093","volume":"119","author":[{"given":"Jan","family":"Gehlen","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, University of Bonn and University Hospital Bonn , Bonn , Germany"},{"name":"Institute of Human Genetics, Philipps University of Marburg , Marburg , Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0001-9634-5908","authenticated-orcid":false,"given":"Anja","family":"Stundl","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Heart Center Bonn, University of Bonn and University Hospital Bonn , Bonn , Germany"},{"name":"Klinik und Poliklinik f\u00fcr Innere Medizin I, Klinikum rechts der Isar, Technical University of Munich , Munich , Germany"},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance , Munich , Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0003-2292-467X","authenticated-orcid":false,"given":"Radoslaw","family":"Debiec","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester , Leicester , UK"},{"name":"NIHR Leicester Biomedical Research Centre, Glenfield Hospital , Leicester , UK"},{"name":"East Midlands Congenital Heart Centre, Glenfield Hospital , Leicester , UK"}]},{"given":"Federica","family":"Fontana","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Biology, Potsdam University , Potsdam , Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0002-5466-9290","authenticated-orcid":false,"given":"Markus","family":"Krane","sequence":"additional","affiliation":[{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance , Munich , Germany"},{"name":"Division of Experimental Surgery, Department of Cardiovascular Surgery, Institute Insure, German Heart Center Munich, TUM School of Medicine, Technical University of Munich , Munich , Germany"},{"name":"Division of Cardiac Surgery, Department of Surgery, Yale University School of Medicine , New Haven, CT , USA"}]},{"given":"Dinara","family":"Sharipova","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Biology, Potsdam University , Potsdam , Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0001-8025-2897","authenticated-orcid":false,"given":"Christopher P","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester , Leicester , UK"},{"name":"NIHR Leicester Biomedical Research Centre, Glenfield Hospital , Leicester , UK"}]},{"given":"Baravan","family":"Al-Kassou","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Heart Center Bonn, University of Bonn and University Hospital Bonn , Bonn , Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0003-2973-2099","authenticated-orcid":false,"given":"Ann-Sophie","family":"Giel","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Philipps University of Marburg , Marburg , Germany"}]},{"given":"Jan-Malte","family":"Sinning","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Heart Center Bonn, University of Bonn and University Hospital Bonn , Bonn , Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0002-4182-7157","authenticated-orcid":false,"given":"Christopher M H","family":"Bruenger","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Philipps University of Marburg , Marburg , Germany"}]},{"given":"Carolin F","family":"Zelck","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Philipps University of Marburg , Marburg , Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0001-9962-0741","authenticated-orcid":false,"given":"Laura L","family":"Koebbe","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Philipps University of Marburg , Marburg , Germany"}]},{"given":"Peter S","family":"Braund","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester , Leicester , UK"},{"name":"NIHR Leicester Biomedical Research Centre, Glenfield Hospital , Leicester , UK"}]},{"ORCID":"http:\/\/orcid.org\/0000-0001-5998-8226","authenticated-orcid":false,"given":"Thomas R","family":"Webb","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester , Leicester , UK"},{"name":"NIHR Leicester Biomedical Research Centre, Glenfield Hospital , Leicester , UK"}]},{"given":"Simon","family":"Hetherington","sequence":"additional","affiliation":[{"name":"Kettering General Hospital NHS Foundation Trust , Kettering , UK"}]},{"ORCID":"http:\/\/orcid.org\/0000-0002-9508-3261","authenticated-orcid":false,"given":"Stephan","family":"Ensminger","sequence":"additional","affiliation":[{"name":"Department of Cardiac and Thoracic Vascular Surgery, University Heart Center L\u00fcbeck, University Hospital of Schleswig-Holstein , L\u00fcbeck , Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg\/Kiel\/L\u00fcbeck , L\u00fcbeck , Germany"}]},{"given":"Buntaro","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Cardiac and Thoracic Vascular Surgery, University Heart Center L\u00fcbeck, University Hospital of Schleswig-Holstein , L\u00fcbeck , Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg\/Kiel\/L\u00fcbeck , L\u00fcbeck , Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0003-4365-8956","authenticated-orcid":false,"given":"Salah A","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Cardiac and Thoracic Vascular Surgery, University Heart Center L\u00fcbeck, University Hospital of Schleswig-Holstein , L\u00fcbeck , Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg\/Kiel\/L\u00fcbeck , L\u00fcbeck , Germany"}]},{"given":"Malakh","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Department of Adult and Pediatric Cardiothoracic Surgery, Vascular Surgery, Heart and Lung Transplantation, Hannover Medical School , Hannover , Germany"}]},{"given":"Heike","family":"Krueger","sequence":"additional","affiliation":[{"name":"Department of Adult and Pediatric Cardiothoracic Surgery, Vascular Surgery, Heart and Lung Transplantation, Hannover Medical School , Hannover , Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0003-3305-9343","authenticated-orcid":false,"given":"Matthias","family":"Siepe","sequence":"additional","affiliation":[{"name":"Heart Center Freiburg\/Bad Krozingen, University Freiburg\/Bad Krozingen , Freiburg , Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0002-0985-9650","authenticated-orcid":false,"given":"Fabian Alexander","family":"Kari","sequence":"additional","affiliation":[{"name":"Heart Center Freiburg\/Bad Krozingen, University Freiburg\/Bad Krozingen , Freiburg , Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0002-2560-4068","authenticated-orcid":false,"given":"Peter","family":"Nordbeck","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik I, University Hospital W\u00fcrzburg , W\u00fcrzburg , Germany"}]},{"given":"Larissa","family":"Buravezky","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik I, University Hospital W\u00fcrzburg , W\u00fcrzburg , Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0003-0060-1052","authenticated-orcid":false,"given":"Malte","family":"Kelm","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Pneumology and Angiology, University Hospital Duesseldorf , Duesseldorf , Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0002-2744-2154","authenticated-orcid":false,"given":"Verena","family":"Veulemans","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Pneumology and Angiology, University Hospital Duesseldorf , Duesseldorf , Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0002-6990-8135","authenticated-orcid":false,"given":"Matti","family":"Adam","sequence":"additional","affiliation":[{"name":"Department of Medicine III, Heart Center Cologne, University Hospital Cologne , Cologne , Germany"}]},{"given":"Stephan","family":"Baldus","sequence":"additional","affiliation":[{"name":"Department of Medicine III, Heart Center Cologne, University Hospital Cologne , Cologne , Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0003-4948-4846","authenticated-orcid":false,"given":"Karl-Ludwig","family":"Laugwitz","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Innere Medizin I, Klinikum rechts der Isar, Technical University of Munich , Munich , Germany"},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance , Munich , Germany"}]},{"given":"Yannick","family":"Haas","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Innere Medizin I, Klinikum rechts der Isar, Technical University of Munich , Munich , Germany"}]},{"given":"Matthias","family":"Karck","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, University Hospital Heidelberg , Heidelberg , Germany"}]},{"given":"Uwe","family":"Mehlhorn","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Helios Klinik Karlsruhe , Karlsruhe , Germany"}]},{"given":"Lars Oliver","family":"Conzelmann","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Helios Klinik Karlsruhe , Karlsruhe , Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0002-5308-1655","authenticated-orcid":false,"given":"Ingo","family":"Breitenbach","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery and Vascular Surgery, Clinic of Braunschweig , Braunschweig , Germany"}]},{"given":"Corinna","family":"Lebherz","sequence":"additional","affiliation":[{"name":"Department of Medicine I, Cardiology\/Angiology\/Intensive Care, University Hospital Aachen , Aachen , Germany"}]},{"given":"Paul","family":"Urbanski","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Cardiovascular Clinic, Rh\u00f6n-Klinikum Campus Bad Neustadt , Neustadt , Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0002-0799-7478","authenticated-orcid":false,"given":"Won-Keun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Center, Kerckhoff Clinic , Bad Nauheim , Germany"}]},{"given":"Joscha","family":"Kandels","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital Leipzig , Leipzig , Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0002-4332-6110","authenticated-orcid":false,"given":"David","family":"Ellinghaus","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel , Kiel , Germany"},{"name":"Novo Nordisk Foundation Center for Protein Research, Disease Systems Biology, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen , Denmark"}]},{"given":"Ulrike","family":"Nowak-Goettl","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Thrombosis and Hemostasis Unit, University Hospital of Kiel and L\u00fcbeck , Kiel , Germany"}]},{"given":"Per","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Bonn and University Hospital Bonn , Bonn , Germany"}]},{"given":"Felix","family":"Wirth","sequence":"additional","affiliation":[{"name":"Division of Experimental Surgery, Department of Cardiovascular Surgery, Institute Insure, German Heart Center Munich, TUM School of Medicine, Technical University of Munich , Munich , Germany"}]},{"given":"Stefanie","family":"Doppler","sequence":"additional","affiliation":[{"name":"Division of Experimental Surgery, Department of Cardiovascular Surgery, Institute Insure, German Heart Center Munich, TUM School of Medicine, Technical University of Munich , Munich , Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0002-4477-3406","authenticated-orcid":false,"given":"Harald","family":"Lahm","sequence":"additional","affiliation":[{"name":"Division of Experimental Surgery, Department of Cardiovascular Surgery, Institute Insure, German Heart Center Munich, TUM School of Medicine, Technical University of Munich , Munich , Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0003-2200-6254","authenticated-orcid":false,"given":"Martina","family":"Dre\u00dfen","sequence":"additional","affiliation":[{"name":"Division of Experimental Surgery, Department of Cardiovascular Surgery, Institute Insure, German Heart Center Munich, TUM School of Medicine, Technical University of Munich , Munich , Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0001-7159-8271","authenticated-orcid":false,"given":"Moritz","family":"von Scheidt","sequence":"additional","affiliation":[{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance , Munich , Germany"},{"name":"Department of Cardiology, German Heart Centre Munich, Technical University of Munich , Munich , Germany"}]},{"given":"Katharina","family":"Knoll","sequence":"additional","affiliation":[{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance , Munich , Germany"},{"name":"Department of Cardiology, German Heart Centre Munich, Technical University of Munich , Munich , Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0003-3326-1621","authenticated-orcid":false,"given":"Thorsten","family":"Kessler","sequence":"additional","affiliation":[{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance , Munich , Germany"},{"name":"Department of Cardiology, German Heart Centre Munich, Technical University of Munich , Munich , Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0002-8284-2994","authenticated-orcid":false,"given":"Christian","family":"Hengstenberg","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna , Vienna , Austria"}]},{"ORCID":"http:\/\/orcid.org\/0000-0001-6428-3001","authenticated-orcid":false,"given":"Heribert","family":"Schunkert","sequence":"additional","affiliation":[{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance , Munich , Germany"},{"name":"Department of Cardiology, German Heart Centre Munich, Technical University of Munich , Munich , Germany"}]},{"given":"Georg","family":"Nickenig","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Heart Center Bonn, University of Bonn and University Hospital Bonn , Bonn , Germany"}]},{"given":"Markus M","family":"N\u00f6then","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Bonn and University Hospital Bonn , Bonn , Germany"}]},{"given":"Aidan P","family":"Bolger","sequence":"additional","affiliation":[{"name":"NIHR Leicester Biomedical Research Centre, Glenfield Hospital , Leicester , UK"},{"name":"East Midlands Congenital Heart Centre, Glenfield Hospital , Leicester , UK"},{"name":"Institute of Biochemistry and Biology, Potsdam University , Potsdam , Germany"}]},{"given":"Salim","family":"Abdelilah-Seyfried","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Biology, Potsdam University , Potsdam , Germany"},{"name":"Institute of Molecular Biology, Hannover Medical School , Hannover , Germany"}]},{"given":"Nilesh J","family":"Samani","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester , Leicester , UK"},{"name":"NIHR Leicester Biomedical Research Centre, Glenfield Hospital , Leicester , UK"}]},{"ORCID":"http:\/\/orcid.org\/0000-0002-4486-6231","authenticated-orcid":false,"given":"Jeanette","family":"Erdmann","sequence":"additional","affiliation":[{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg\/Kiel\/L\u00fcbeck , L\u00fcbeck , Germany"},{"name":"Institute for Cardiogenetics, University Heart Centre L\u00fcbeck, University of L\u00fcbeck , L\u00fcbeck , Germany"}]},{"given":"Teresa","family":"Trenkwalder","sequence":"additional","affiliation":[{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance , Munich , Germany"},{"name":"Department of Cardiology, German Heart Centre Munich, Technical University of Munich , Munich , Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0001-9217-6457","authenticated-orcid":false,"given":"Johannes","family":"Schumacher","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Bonn and University Hospital Bonn , Bonn , Germany"},{"name":"Institute of Human Genetics, Philipps University of Marburg , Marburg , Germany"}]}],"member":"286","published-online":{"date-parts":[[2022,6,21]]},"reference":[{"key":"2023050214511111700_cvac099-B1","doi-asserted-by":"crossref","first-page":"2789","DOI":"10.1016\/j.jacc.2009.12.068","article-title":"Bicuspid aortic valve disease","volume":"55","author":"Siu","year":"2010","journal-title":"J Am Coll Cardiol"},{"key":"2023050214511111700_cvac099-B2","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1136\/heart.83.1.81","article-title":"Clinical significance of the bicuspid aortic valve","volume":"83","author":"Ward","year":"2000","journal-title":"Heart"},{"key":"2023050214511111700_cvac099-B3","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1161\/01.CIR.0000155623.48408.C5","article-title":"Frequency by decades of unicuspid, bicuspid, and tricuspid aortic valves in adults having isolated aortic valve replacement for aortic stenosis, with or without associated aortic regurgitation","volume":"111","author":"Roberts","year":"2005","journal-title":"Circulation"},{"key":"2023050214511111700_cvac099-B4","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.jacc.2004.03.050","article-title":"Bicuspid aortic valve is heritable","volume":"44","author":"Cripe","year":"2004","journal-title":"J Am Coll Cardiol"},{"key":"2023050214511111700_cvac099-B5","first-page":"603","article-title":"Familial clustering of bicuspid aortic valve and its relationship with aortic dilation in first-degree relatives","volume":"105","author":"Galian-Gay","year":"2019","journal-title":"Heart"},{"key":"2023050214511111700_cvac099-B6","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1038\/ng.2007.6","article-title":"Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections","volume":"39","author":"Guo","year":"2007","journal-title":"Nat Genet"},{"key":"2023050214511111700_cvac099-B7","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/ng1511","article-title":"A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2","volume":"37","author":"Loeys","year":"2005","journal-title":"Nat Genet"},{"key":"2023050214511111700_cvac099-B8","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/nature03940","article-title":"Mutations in NOTCH1 cause aortic valve disease","volume":"437","author":"Garg","year":"2005","journal-title":"Nature"},{"key":"2023050214511111700_cvac099-B9","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/s41588-018-0265-y","article-title":"ROBO4 variants predispose individuals to bicuspid aortic valve and thoracic aortic aneurysm","volume":"51","author":"Gould","year":"2019","journal-title":"Nat Genet"},{"key":"2023050214511111700_cvac099-B10","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1002\/humu.22030","article-title":"Nonsynonymous variants in the SMAD6 gene predispose to congenital cardiovascular malformation","volume":"33","author":"Tan","year":"2012","journal-title":"Hum Mutat"},{"key":"2023050214511111700_cvac099-B11","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/s41588-019-0536-2","article-title":"Loss of ADAMTS19 causes progressive non-syndromic heart valve disease","volume":"52","author":"Wunnemann","year":"2020","journal-title":"Nat Genet"},{"key":"2023050214511111700_cvac099-B12","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/j.jacc.2014.04.073","article-title":"A roadmap to investigate the genetic basis of bicuspid aortic valve and its complications: insights from the International BAVCon (Bicuspid Aortic Valve Consortium)","volume":"64","author":"Prakash","year":"2014","journal-title":"J Am Coll Cardiol"},{"key":"2023050214511111700_cvac099-B13","doi-asserted-by":"crossref","first-page":"15481","DOI":"10.1038\/ncomms15481","article-title":"Protein-altering and regulatory genetic variants near GATA4 implicated in bicuspid aortic valve","volume":"8","author":"Yang","year":"2017","journal-title":"Nat Commun"},{"key":"2023050214511111700_cvac099-B14","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1038\/s41467-018-03252-6","article-title":"Genome-wide analysis yields new loci associating with aortic valve stenosis","volume":"9","author":"Helgadottir","year":"2018","journal-title":"Nat Commun"},{"key":"2023050214511111700_cvac099-B15","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1067\/mhj.2002.123579","article-title":"Assessment of clinically silent atherosclerotic disease and established and novel risk factors for predicting myocardial infarction and cardiac death in healthy middle-aged subjects: rationale and design of the Heinz Nixdorf RECALL study. Risk factors, evaluation of coronary calcium and lifestyle","volume":"144","author":"Schmermund","year":"2002","journal-title":"Am Heart J"},{"key":"2023050214511111700_cvac099-B16","doi-asserted-by":"crossref","first-page":"e1001779","DOI":"10.1371\/journal.pmed.1001779","article-title":"UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age","volume":"12","author":"Sudlow","year":"2015","journal-title":"PLoS Med"},{"key":"2023050214511111700_cvac099-B17","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1038\/ng.3656","article-title":"Next-generation genotype imputation service and methods","volume":"48","author":"Das","year":"2016","journal-title":"Nat Genet"},{"key":"2023050214511111700_cvac099-B18","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/s41586-021-03205-y","article-title":"Sequencing of;53,831, diverse genomes from the NHLBI TOPMed program","volume":"590","author":"Taliun","year":"2021","journal-title":"Nature"},{"key":"2023050214511111700_cvac099-B19","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1093\/bioinformatics\/btu704","article-title":"minimac2: faster genotype imputation","volume":"31","author":"Fuchsberger","year":"2015","journal-title":"Bioinformatics"},{"key":"2023050214511111700_cvac099-B20","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1038\/ng.3643","article-title":"A reference panel of 64,976 haplotypes for genotype imputation","volume":"48","author":"McCarthy","year":"2016","journal-title":"Nat Genet"},{"key":"2023050214511111700_cvac099-B21","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms9111","article-title":"Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel","volume":"6","author":"Huang","year":"2015","journal-title":"Nat Commun"},{"key":"2023050214511111700_cvac099-B22","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second-generation PLINK: rising to the challenge of larger and richer datasets","volume":"4","author":"Chang","year":"2015","journal-title":"Gigascience"},{"key":"2023050214511111700_cvac099-B23","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1093\/bioinformatics\/btq340","article-title":"METAL: fast and efficient meta-analysis of genomewide association scans","volume":"26","author":"Willer","year":"2010","journal-title":"Bioinformatics"},{"key":"2023050214511111700_cvac099-B24","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/ng.2213","article-title":"Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits","volume":"44","author":"Yang","year":"2012","journal-title":"Nat Genet"},{"key":"2023050214511111700_cvac099-B25","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ajhg.2010.11.011","article-title":"GCTA: a tool for genome-wide complex trait analysis","volume":"88","author":"Yang","year":"2011","journal-title":"Am J Hum Genet"},{"key":"2023050214511111700_cvac099-B26","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1038\/ng.3406","article-title":"An atlas of genetic correlations across human diseases and traits","volume":"47","author":"Bulik-Sullivan","year":"2015","journal-title":"Nat Genet"},{"key":"2023050214511111700_cvac099-B27","doi-asserted-by":"crossref","first-page":"eaba7721","DOI":"10.1126\/science.aba7721","article-title":"A human cell atlas of fetal gene expression","volume":"370","author":"Cao","year":"2020","journal-title":"Science"},{"key":"2023050214511111700_cvac099-B28","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1038\/s41467-017-01261-5","article-title":"Functional mapping and annotation of genetic associations with FUMA","volume":"8","author":"Watanabe","year":"2017","journal-title":"Nat Commun"},{"key":"2023050214511111700_cvac099-B29","doi-asserted-by":"crossref","first-page":"3222","DOI":"10.1038\/s41467-019-11181-1","article-title":"Genetic mapping of cell type specificity for complex traits","volume":"10","author":"Watanabe","year":"2019","journal-title":"Nat Commun"},{"key":"2023050214511111700_cvac099-B30","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.devcel.2019.01.005","article-title":"Population and single-cell analysis of human cardiogenesis reveals unique LGR5 ventricular progenitors in embryonic outflow tract","volume":"48","author":"Sahara","year":"2019","journal-title":"Dev Cell"},{"key":"2023050214511111700_cvac099-B31","doi-asserted-by":"crossref","first-page":"e141837","DOI":"10.1172\/JCI141837","article-title":"Congenital heart disease risk loci identified by genome-wide association study in European patients","volume":"131","author":"Lahm","year":"2021","journal-title":"J Clin Invest"},{"key":"2023050214511111700_cvac099-B32","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"2023050214511111700_cvac099-B33","doi-asserted-by":"crossref","first-page":"W537","DOI":"10.1093\/nar\/gky379","article-title":"The galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2018 update","volume":"46","author":"Afgan","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"2023050214511111700_cvac099-B34","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: an efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"2023050214511111700_cvac099-B35","doi-asserted-by":"crossref","first-page":"14049","DOI":"10.1038\/ncomms14049","article-title":"Massively parallel digital transcriptional profiling of single cells","volume":"8","author":"Zheng","year":"2017","journal-title":"Nat Commun"},{"key":"2023050214511111700_cvac099-B36","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Hao","year":"2021","journal-title":"Cell"},{"key":"2023050214511111700_cvac099-B37","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nbt.4096","article-title":"Integrating single-cell transcriptomic data across different conditions, technologies, and species","volume":"36","author":"Butler","year":"2018","journal-title":"Nat Biotechnol"},{"key":"2023050214511111700_cvac099-B38","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive integration of single-cell data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"2023050214511111700_cvac099-B39","doi-asserted-by":"crossref","first-page":"5199","DOI":"10.1242\/dev.02087","article-title":"Cellular and molecular analyses of vascular tube and lumen formation in zebrafish","volume":"132","author":"Jin","year":"2005","journal-title":"Development"},{"key":"2023050214511111700_cvac099-B40","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1006\/scdb.1997.0173","article-title":"An on-line database for zebrafish development and genetics research","volume":"8","author":"Westerfield","year":"1997","journal-title":"Semin Cell Dev Biol"},{"key":"2023050214511111700_cvac099-B41","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nature"},{"key":"2023050214511111700_cvac099-B42","doi-asserted-by":"crossref","first-page":"107883","DOI":"10.1016\/j.celrep.2020.107883","article-title":"Antagonistic activities of Vegfr3\/Flt4 and Notch1b fine-tune mechanosensitive signaling during zebrafish cardiac valvulogenesis","volume":"32","author":"Fontana","year":"2020","journal-title":"Cell Rep"},{"key":"2023050214511111700_cvac099-B43","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.devcel.2014.12.016","article-title":"Regulation of beta1 integrin-Klf2-mediated angiogenesis by CCM proteins","volume":"32","author":"Renz","year":"2015","journal-title":"Dev Cell"},{"key":"2023050214511111700_cvac099-B44","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/j.devcel.2013.01.026","article-title":"Unilateral dampening of Bmp activity by nodal generates cardiac left-right asymmetry","volume":"24","author":"Veerkamp","year":"2013","journal-title":"Dev Cell"},{"key":"2023050214511111700_cvac099-B45","doi-asserted-by":"crossref","first-page":"4193","DOI":"10.1242\/dev.01970","article-title":"Genetic and cellular analyses of zebrafish atrioventricular cushion and valve development","volume":"132","author":"Beis","year":"2005","journal-title":"Development"},{"key":"2023050214511111700_cvac099-B46","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1002\/(SICI)1096-8628(19990319)83:3<201::AID-AJMG11>3.0.CO;2-V","article-title":"GATA4 haploinsufficiency in patients with interstitial deletion of chromosome region 8p23.1 and congenital heart disease","volume":"83","author":"Pehlivan","year":"1999","journal-title":"Am J Med Genet"},{"key":"2023050214511111700_cvac099-B47","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1002\/1096-8628(20011115)104:1<79::AID-AJMG1598>3.0.CO;2-T","article-title":"Inherited duplication, dup (8) (p23.1p23.1) pat, in a father and daughter with congenital heart defects","volume":"104","author":"Kennedy","year":"2001","journal-title":"Am J Med Genet"},{"key":"2023050214511111700_cvac099-B48","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/nature01827","article-title":"GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5","volume":"424","author":"Garg","year":"2003","journal-title":"Nature"},{"key":"2023050214511111700_cvac099-B49","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1136\/jmg.2007.052183","article-title":"GATA4 sequence variants in patients with congenital heart disease","volume":"44","author":"Tomita-Mitchell","year":"2007","journal-title":"J Med Genet"},{"key":"2023050214511111700_cvac099-B50","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.ejmg.2008.06.005","article-title":"GATA4 mutations in 486 Chinese patients with congenital heart disease","volume":"51","author":"Zhang","year":"2008","journal-title":"Eur J Med Genet"},{"key":"2023050214511111700_cvac099-B51","doi-asserted-by":"crossref","first-page":"e62138","DOI":"10.1371\/journal.pone.0062138","article-title":"Identification of functional mutations in GATA4 in patients with congenital heart disease","volume":"8","author":"Wang","year":"2013","journal-title":"PLoS One"},{"key":"2023050214511111700_cvac099-B52","doi-asserted-by":"crossref","first-page":"e44706","DOI":"10.7554\/eLife.44706","article-title":"Mechanically activated piezo channels modulate outflow tract valve development through the Yap1 and Klf2-Notch signaling axis","volume":"8","author":"Duchemin","year":"2019","journal-title":"Elife"},{"key":"2023050214511111700_cvac099-B53","doi-asserted-by":"crossref","first-page":"945","DOI":"10.2174\/15680096113136660100","article-title":"Emerging role of mucins in epithelial to mesenchymal transition","volume":"13","author":"Ponnusamy","year":"2013","journal-title":"Curr Cancer Drug Targets"},{"key":"2023050214511111700_cvac099-B54","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.bbrc.2016.12.020","article-title":"MiR-211 inhibits invasion and epithelial-to-mesenchymal transition (EMT) of cervical cancer cells via targeting MUC4","volume":"485","author":"Xu","year":"2017","journal-title":"Biochem Biophys Res Commun"},{"key":"2023050214511111700_cvac099-B55","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.bbadis.2016.02.006","article-title":"Notch-dependent EMT is attenuated in patients with aortic aneurysm and bicuspid aortic valve","volume":"1862","author":"Kostina","year":"2016","journal-title":"Biochim Biophys Acta"},{"key":"2023050214511111700_cvac099-B56","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1161\/CIRCRESAHA.111.259960","article-title":"Endocardial and epicardial epithelial to mesenchymal transitions in heart development and disease","volume":"110","author":"von Gise","year":"2012","journal-title":"Circ Res"},{"key":"2023050214511111700_cvac099-B57","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3390\/jcm5020027","article-title":"Epicardial epithelial-to-mesenchymal transition in heart development and disease","volume":"5","author":"Krainock","year":"2016","journal-title":"J Clin Med"},{"key":"2023050214511111700_cvac099-B58","doi-asserted-by":"crossref","first-page":"802930","DOI":"10.3389\/fcvm.2021.802930","article-title":"Development of the human arterial valves: understanding bicuspid aortic valve","volume":"8","author":"Henderson","year":"2021","journal-title":"Front Cardiovasc Med"},{"key":"2023050214511111700_cvac099-B59","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.yjmcc.2013.03.010","article-title":"Insufficient versican cleavage and Smad2 phosphorylation results in bicuspid aortic and pulmonary valves","volume":"60","author":"Dupuis","year":"2013","journal-title":"J Mol Cell Cardiol"},{"key":"2023050214511111700_cvac099-B60","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1038\/onc.2015.327","article-title":"Mice deficient in Muc4 are resistant to experimental colitis and colitis-associated colorectal cancer","volume":"35","author":"Das","year":"2016","journal-title":"Oncogene"},{"key":"2023050214511111700_cvac099-B61","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/onc.2017.327","article-title":"Membrane Mucin Muc4 promotes blood cell association with tumor cells and mediates efficient metastasis in a mouse model of breast cancer","volume":"37","author":"Rowson-Hodel","year":"2018","journal-title":"Oncogene"},{"key":"2023050214511111700_cvac099-B62","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.semcdb.2010.09.011","article-title":"ErbB signaling in cardiac development and disease","volume":"21","author":"Sanchez-Soria","year":"2010","journal-title":"Semin Cell Dev Biol"}],"container-title":["Cardiovascular Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cardiovascres\/advance-article-pdf\/doi\/10.1093\/cvr\/cvac099\/44362966\/cvac099.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cardiovascres\/article-pdf\/119\/3\/857\/50169473\/cvac099.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cardiovascres\/article-pdf\/119\/3\/857\/50169473\/cvac099.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T15:19:37Z","timestamp":1683040777000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cardiovascres\/article\/119\/3\/857\/6612701"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,21]]},"references-count":62,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,6,21]]},"published-print":{"date-parts":[[2023,5,2]]}},"URL":"http:\/\/dx.doi.org\/10.1093\/cvr\/cvac099","relation":{},"ISSN":["0008-6363","1755-3245"],"issn-type":[{"value":"0008-6363","type":"print"},{"value":"1755-3245","type":"electronic"}],"subject":["Physiology (medical)","Cardiology and Cardiovascular Medicine","Physiology"],"published-other":{"date-parts":[[2023,3,1]]},"published":{"date-parts":[[2022,6,21]]}}} |