ArticleNature genetics2015
Genetic association analyses highlight biological pathways underlying mitral valve prolapse.
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In one paragraph
Article in Nature genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 2 of them syntheses that pooled it.
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83citing papers in PubMed, 2 pooled it
7.6field-weighted citation impact, top 2% of its field
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Who cites it
83 citing papers in PubMed, 2 syntheses or guidelines pooled it, 130 citations in OpenAlex.
- Genome-wide association study reveals novel genetic loci: a new polygenic risk score for mitral valve prolapse.European heart journal · 2022Pooled it
- Genome-Wide Association Meta-Analysis Supports Genes Involved in Valve and Cardiac Development to Associate With Mitral Valve Prolapse.Circulation. Genomic and precision medicine · 2021Pooled it
- Re-analysis of single-cell transcriptomics reveals a critical role of TNS1 gene in driving contractile VSMC transdifferentiation into macrophage-like SMC and atherosclerotic plaque instability.Clinical and translational medicine · 2026Article
- Recent advances in omics-based research of mitral valve disease.Frontiers in cardiovascular medicine · 2026Review
- Connective tissue disorders and cardiac arrhythmias: genetic pathways, mechanistic bridges, and clinical implications.Frontiers in cardiovascular medicine · 2026Review
- Broadening horizons: new links between cilia and heart development and disease.Frontiers in cardiovascular medicine · 2026Review
- Mechanisms of mitral valve development and disease.Frontiers in cardiovascular medicine · 2026Review
- Multimodality cardiovascular imaging in arrhythmic mitral valve prolapse: a state-of-the-art review from structural assessment to myocardial tissue characterization.Frontiers in cardiovascular medicine · 2026Review
- Zebrafish in Cardiovascular Disease Research: from Model to Application.International journal of biological sciences · 2026Review
- A zebrafish model of chronic heart failure caused by protein aggregation in heart valves.Communications biology · 2025Article
- Mitral Valve Prolapse and Sudden Cardiac Death-A Puzzle with Missing Pieces: Review of the Literature and Case Report.Medical sciences (Basel, Switzerland) · 2025Review
- Identifying cross-tissue molecular targets of lung function by multi-omics integration analysis from DNA methylation and gene expression of diverse human tissues.BMC genomics · 2025Article
- Recessive genetic contribution to congenital heart disease in 5,424 probands.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Molecular convergence of risk variants for congenital heart defects leveraging a regulatory map of the human fetal heart.medRxiv : the preprint server for health sciences · 2024Article
- Unraveling the Mechanisms of Valvular Heart Disease to Identify Medical Therapy Targets: A Scientific Statement From the American Heart Association.Circulation · 2024Review
- Mendelian randomization reveals interactions of the blood proteome and immunome in mitral valve prolapse.Communications medicine · 2024Article
- Arrhythmic Mitral Valve Prolapse Phenotype: An Unsupervised Machine Learning Analysis Using a Multicenter Cardiac MRI Registry.Radiology. Cardiothoracic imaging · 2024Article
- Degenerative Mitral Regurgitation Outcomes in Asian Compared With European-American Institutions.JACC. Asia · 2024Article
- Insights into the Inherited Basis of Valvular Heart Disease.Current cardiology reports · 2024Review
- Valvulopathies and Genetics: Where are We?Reviews in cardiovascular medicine · 2024Review
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
42 authors at 12 institutions in 6 countries.
Christian DinaINSERM Unité Mixte de Recherche (UMR) 1087, Centre National de la Recherche Scientifique (CNRS) UMR 6291, Institut du Thorax, Nantes, France.ORCID http://orcid.org/0000-0002-7722-7348
Nabila Bouatia-NajiINSERM UMR 970, Paris Cardiovascular Research Center, Paris, France.
Nathan TuckerCardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
Francesca N DellingFramingham Heart Study, Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, US National Institutes of Health, Framingham, Massachusetts, USA.
Katelynn ToomerDepartment of Regenerative Medicine and Cell Biology, Cardiovascular Developmental Biology Center, Children's Research Institute, Medical University of South Carolina, Charleston, South Carolina, USA.
Ronen DurstDepartment of Cardiology, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
Maelle PerrocheauINSERM UMR 970, Paris Cardiovascular Research Center, Paris, France.
Leticia Fernandez-FrieraHospital Universitario Montepríncipe, Universidad Centro de Estudios Universitarios (CEU) San Pablo, Madrid, Spain.
Jorge SolisHospital Universitario Montepríncipe, Universidad Centro de Estudios Universitarios (CEU) San Pablo, Madrid, Spain.ORCID http://orcid.org/0000-0002-4227-7062
PROMESA investigators
Thierry Le TourneauINSERM Unité Mixte de Recherche (UMR) 1087, Centre National de la Recherche Scientifique (CNRS) UMR 6291, Institut du Thorax, Nantes, France.
Ming-Huei ChenFramingham Heart Study, Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, US National Institutes of Health, Framingham, Massachusetts, USA.
Vincent ProbstINSERM Unité Mixte de Recherche (UMR) 1087, Centre National de la Recherche Scientifique (CNRS) UMR 6291, Institut du Thorax, Nantes, France.
Yohan BosseInstitut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Quebec City, Quebec, Canada.
Philippe PibarotInstitut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Quebec City, Quebec, Canada.
Diana ZelenikaCentre National de Génotypage, Evry, France.
Mark LathropCentre National de Génotypage, Evry, France.
Serge HercbergParis Descartes University, Paris Sorbonne Cité, Paris, France.
Ronan RousselParis Diderot University, Paris, France.
Emelia J BenjaminFramingham Heart Study, Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, US National Institutes of Health, Framingham, Massachusetts, USA.ORCID http://orcid.org/0000-0003-4076-2336
Fabrice BonnetINSERM, Clinical Investigation Centre (CIC) 0203, University Hospital of Pontchaillou, Rennes, France.
Su Hao LoDepartment of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, Davis, California, USA.
Elena DolmatovaCardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
Floriane SimonetINSERM Unité Mixte de Recherche (UMR) 1087, Centre National de la Recherche Scientifique (CNRS) UMR 6291, Institut du Thorax, Nantes, France.
Simon LecointeINSERM Unité Mixte de Recherche (UMR) 1087, Centre National de la Recherche Scientifique (CNRS) UMR 6291, Institut du Thorax, Nantes, France.
Florence KyndtINSERM Unité Mixte de Recherche (UMR) 1087, Centre National de la Recherche Scientifique (CNRS) UMR 6291, Institut du Thorax, Nantes, France.
Richard RedonINSERM Unité Mixte de Recherche (UMR) 1087, Centre National de la Recherche Scientifique (CNRS) UMR 6291, Institut du Thorax, Nantes, France.
Hervé Le MarecINSERM Unité Mixte de Recherche (UMR) 1087, Centre National de la Recherche Scientifique (CNRS) UMR 6291, Institut du Thorax, Nantes, France.
Philippe FroguelCNRS UMR 8199, Lille Pasteur Institute, Lille 2 University, European Genomic Institute for Diabetes (EGID), Lille, France.
Patrick T EllinorCardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts, USA.ORCID http://orcid.org/0000-0002-2067-0533
Ramachandran S VasanFramingham Heart Study, Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, US National Institutes of Health, Framingham, Massachusetts, USA.
Patrick BrunevalINSERM UMR 970, Paris Cardiovascular Research Center, Paris, France.
Roger R MarkwaldDepartment of Regenerative Medicine and Cell Biology, Cardiovascular Developmental Biology Center, Children's Research Institute, Medical University of South Carolina, Charleston, South Carolina, USA.
Russell A NorrisDepartment of Regenerative Medicine and Cell Biology, Cardiovascular Developmental Biology Center, Children's Research Institute, Medical University of South Carolina, Charleston, South Carolina, USA.
David J MilanCardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
Susan A SlaugenhauptCenter for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Robert A LevineCardiac Ultrasound Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Jean-Jacques SchottINSERM Unité Mixte de Recherche (UMR) 1087, Centre National de la Recherche Scientifique (CNRS) UMR 6291, Institut du Thorax, Nantes, France.
Albert A HagegeINSERM UMR 970, Paris Cardiovascular Research Center, Paris, France.
MVP-France
Xavier JeunemaitreINSERM UMR 970, Paris Cardiovascular Research Center, Paris, France.ORCID http://orcid.org/0000-0001-5925-381X
Leducq Transatlantic MITRAL Network
Centre National de la Recherche Scientifique · FRDélégation Paris 5 · FRBeth Israel Deaconess Medical Center · USHarvard University · USInserm · FRUniversidad San Pablo CEU · ESBoston University · USBroad Institute · USGenome Canada · CAHadassah Medical Center · ILMassachusetts General Hospital · USMedical University of South Carolina · US
Funding
PHARMACOGENOMICS OF ARRHYTHMIA THERAPYU01HL065962 · NHLBI · VANDERBILT UNIVERSITY · PI RODEN, DAN M · 2001 to 2009
$24.8MIDENTIFICATION OF COMMON GENETIC VARIANTS FOR ATRIAL FIBRILLATION AND PR INTERVALR01HL092577 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI BENJAMIN, EMELIA J., ELLINOR, PATRICK THOMAS · 2009 to 2025
$20.6MPharmacogenomics of Arrhythmia TherapyU19HL065962 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RODEN, DAN M · 2010 to 2014
$17.4MMULTIDISCIPLINARY RESEARCH TRAINING IN CARDIOLOGYT32HL007208 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Patrick Thomas Ellinor, David E Sosnovik · 1985 to 2026
$16.1MTargeted Nano-therapeutics for Neural RegenerationP20GM103444 · NIGMS · CLEMSON UNIVERSITY · PI SIMIONESCU, AGNETA · 2012 to 2018
$14.9MSC COBRE for Developmentally Based Cardiovascular DiseasesP30GM103342 · NIGMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI MARKWALD, ROGER R · 2012 to 2016
$5.5MMUCOPOLYSACCHRIDE METABOLISM IN CARDIAC ANOMALIESR01HL033756 · NHLBI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI MARKWALD, ROGER R · 1985 to 2015
$4.8MEffect of Mitral Regurgitation on Ischemic LV RemodelingR01HL072265 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI LEVINE, ROBERT A · 2003 to 2013
$3.5MImproving Mitral Compensation in Ischemic RegurgitationR01HL109506 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI AIKAWA, ELENA, BISCHOFF, JOYCE E. · 2012 to 2015
$3.3MGenetics and Mechanisms of Mitral Valve ProlapseR01HL127692 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI MILAN, DAVID J, SLAUGENHAUPT, SUSAN A · 2015 to 2018
$3.0MEXTRAMURAL RESEARCH FACILITIES CONSTRUCTIONC06RR018823 · NCRR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI RAYMOND, JOHN R · 2003 to 2003
$2.9MTreating Ventricle and Valve: New Synergies for Ischemic LV Remodeling with MRR01HL128099 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI AKAR, FADI GABRIEL, LEVINE, ROBERT A · 2016 to 2019
$2.8MCIHR MOP-102481CIHR MOP-102737CIHR MOP-114997CIHR MOP-126072CIHR MOP-137058NCRR NIH HHS C06 RR018823NHLBI NIH HHS HL065962NHLBI NIH HHS HL092577NHLBI NIH HHS HL104156NHLBI NIH HHS HL109506NHLBI NIH HHS K23 HL116652NHLBI NIH HHS K24 HL067434NHLBI NIH HHS K24 HL105780NHLBI NIH HHS K24HL105780NHLBI NIH HHS K24 HL67434NHLBI NIH HHS R01 HL072265NHLBI NIH HHS R01 HL092577NHLBI NIH HHS R01 HL104156NHLBI NIH HHS R01 HL109004NHLBI NIH HHS R01 HL109506NHLBI NIH HHS R01 HL127692NHLBI NIH HHS R01-HL127692NHLBI NIH HHS R01 HL128099NHLBI NIH HHS R01-HL33756NHLBI NIH HHS R01 HL72265NHLBI NIH HHS T32 HL007208NHLBI NIH HHS U01 HL065962NHLBI NIH HHS U19 HL065962NIGMS NIH HHS 1P30 GM103342NIGMS NIH HHS 8P20 GM103444-07
Abstract
Nonsyndromic mitral valve prolapse (MVP) is a common degenerative cardiac valvulopathy of unknown etiology that predisposes to mitral regurgitation, heart failure and sudden death. Previous family and pathophysiological studies suggest a complex pattern of inheritance. We performed a meta-analysis of 2 genome-wide association studies in 1,412 MVP cases and 2,439 controls. We identified 6 loci, which we replicated in 1,422 cases and 6,779 controls, and provide functional evidence for candidate genes. We highlight LMCD1 (LIM and cysteine-rich domains 1), which encodes a transcription factor and for which morpholino knockdown of the ortholog in zebrafish resulted in atrioventricular valve regurgitation. A similar zebrafish phenotype was obtained with knockdown of the ortholog of TNS1, which encodes tensin 1, a focal adhesion protein involved in cytoskeleton organization. We also showed expression of tensin 1 during valve morphogenesis and describe enlarged posterior mitral leaflets in Tns1(-/-) mice. This study identifies the first risk loci for MVP and suggests new mechanisms involved in mitral valve regurgitation, the most common indication for mitral valve repair.
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AnimalsCase-Control StudiesGenome-Wide Association StudyHumansMiceMitral Valve Prolapse
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