SynthesisNature genetics2026
Genomic and transcriptomic analyses of aortic stenosis enhance therapeutic target discovery and disease prediction.
Abstract readMeta-Analysis
In one paragraph
Synthesis in Nature genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed.
- LINE-1 Deregulation in Ovarian Cancer: Implications for Diagnosis, Prognosis, and Therapeutic Targeting.Molecular diagnosis & therapy · 2026Review
- Aortic Stenosis Hyalectan Remodeling Revealed by Proteomics and Glycoproteomics.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Biatrial Inflammatory and Fibrotic Remodeling in Severe Aortic Stenosis Compared with CABG Controls.Metabolites · 2026Article
- Lipoprotein(a), Inflammation, and Risk of Coronary Artery Disease and Aortic Valve Stenosis.JAMA cardiology · 2026Article
- Aortic valve stenosis serum IGFBP2 mediates female-specific Evogliptin resistance in valve myofibroblasts.Cell reports · 2026Article
- Digital phenotyping of aortic stenosis-related remodeling reveals complementary structural, electrical, and hemodynamic signatures.medRxiv : the preprint server for health sciences · 2026Article
- Genetic factors contributing to atherosclerosis.Current opinion in cardiology · 2026Review
- Genetic studies of aortic stenosis provide a broader view of narrowed valves.Nature cardiovascular research · 2026Article
- Familial Hypercholesterolemia.Methodist DeBakey cardiovascular journal · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
105 authors.
Aeron M SmallDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Ta-Yu Yang *McGill University Health Centre and Research Institute, Montréal, Quebec, Canada.ORCID 0000-0002-5379-5340
Shinsuke Itoh *Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-9567-8188
Sébastien Thériault *Institut Universitaire de Cardiologie et de Pneumologie de Québec-Université Laval, Quebec City, Quebec, Canada.ORCID 0000-0003-1893-8307
Line Dufresne *McGill University Health Centre and Research Institute, Montréal, Quebec, Canada.ORCID 0000-0001-6923-8517
Ryo KurosawaLaboratory for Cardiovascular Genomics and Informatics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Issei KomuroInternational University of Health and Welfare, Tokyo, Japan.
Koichi MatsudaInstitute of Medical Science, Laboratory of Genome Technology, Human Genome Center, The University of Tokyo, Tokyo, Japan.ORCID 0000-0001-7292-2686
Ha My T VyThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Eric H Farber-EgerDepartment of Medicine, Division of Cardiology, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID 0000-0003-0281-3796
Lauren Lee ShafferDepartment of Medicine, Division of Cardiology, Vanderbilt University Medical Center, Nashville, TN, USA.
Kristin M BoulierDivision of Cardiology, Department of Medicine, Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA.
Kristin M CoreyDuke Molecular Physiology Institute, Duke University, Durham, NC, USA.
Megan E RamakerDuke Molecular Physiology Institute, Duke University, Durham, NC, USA.
Fabien LaporteNantes Université, CHU Nantes, CNRS, INSERM, l'institut du Thorax, Nantes, France.ORCID 0000-0003-2509-3293
Jean-Jacques SchottNantes Université, CHU Nantes, CNRS, INSERM, l'institut du Thorax, Nantes, France.ORCID 0000-0002-9578-9475
Solena Le ScouarnecNantes Université, CHU Nantes, CNRS, INSERM, l'institut du Thorax, Nantes, France.ORCID 0000-0003-3444-2125
Sasha A SinghDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Abhijeet R SonawaneDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Harry A SmithColorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Nicholas RafaelsColorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Colorado Center for Personalized Medicine
Jonas GhouseDepartment of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.ORCID 0000-0002-9634-5964
Anna A RajaDepartment of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Sisse R OstrowskiDepartment of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.ORCID 0000-0001-5288-3851
Erik SørensenDepartment of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.ORCID 0000-0002-5002-9077
Christina MikkelsenDepartment of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.ORCID 0000-0002-2945-6197
Ole B PedersenDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0003-2312-5976
Christian ErikstrupDepartment of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark.ORCID 0000-0001-6551-6647
Henrik UllumStatens Serum Institut, Copenhagen, Denmark.
DBDS Genomic Consortium
Gardar SveinbjornssondeCODE genetics/Amgen, Inc., Reykjavik, Iceland.
Daniel F GudbjartssondeCODE genetics/Amgen, Inc., Reykjavik, Iceland.
Erik AbnerEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.ORCID 0000-0002-6529-3161
Estonian Biobank Research Team
Jiwoo LeeProgram in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0003-0555-585X
Andrea GannaInstitute for Molecular Medicine Finland, HiLIFE, University of Helsinki, Helsinki, Finland.ORCID 0000-0002-8147-240X
Ulrike Nowak-GöttlThrombosis and Hemostasis Unit, Institute of Clinical Chemistry, University Hospital Kiel, Kiel, Germany.
Sarah FinerWolfson Institute of Population Health, Queen Mary University of London, London, UK.ORCID 0000-0002-2684-4653
Genes & Health Research Team
Johannes SchumacherInstitute of Human Genetics, Philipps University of Marburg, Marburg, Germany.ORCID 0000-0001-9217-6457
Carlo MajInstitute of Human Genetics, Philipps University of Marburg, Marburg, Germany.ORCID 0000-0002-9559-1725
Baravan Al-KassouDepartment of Medicine II, Heart Center Bonn, University of Bonn and University Hospital Bonn, Bonn, Germany.
Georg NickenigDepartment of Medicine II, Heart Center Bonn, University of Bonn and University Hospital Bonn, Bonn, Germany.
Teresa TrenkwalderDepartment of Cardiology, German Heart Centre Munich, TUM University Hospital, School of Medicine and Health, Technical University of Munich, Munich, Germany.
Martina DreβenDepartment of Cardiovascular Surgery, Institute Insure, German Heart Center Munich, School of Medicine & Health, TUM University Hospital, Technical University of Munich, Munich, Germany.ORCID 0000-0003-2200-6254
Markus KraneDZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
Markus M NöthenInstitute of Human Genetics, University of Bonn and University Hospital Bonn, Bonn, Germany.
Marta R MoksnesHUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, NTNU Norwegian University of Science and Technology, Trondheim, Norway.ORCID 0000-0002-2690-5153
Ben M BrumptonHUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, NTNU Norwegian University of Science and Technology, Trondheim, Norway.ORCID 0000-0002-3058-1059
Stacey KnightIntermountain Healthcare, Salt Lake City, UT, USA.ORCID 0000-0003-0092-7327
Kirk U KnowltonIntermountain Healthcare, Salt Lake City, UT, USA.
Lincoln NadauldIntermountain Healthcare, Salt Lake City, UT, USA.
Radek DebiecDepartment of Cardiovascular Sciences, University of Leicester, Leicester, UK.
Muntaser D MusamehDepartment of Cardiovascular Sciences, University of Leicester, Leicester, UK.
Peter S BraundDepartment of Cardiovascular Sciences, University of Leicester, Leicester, UK.ORCID 0000-0001-8540-5709
Christopher P NelsonDepartment of Cardiovascular Sciences, University of Leicester, Leicester, UK.
Tomasz CzubaThe Wallenberg Laboratory/Department of Molecular and Clinical Medicine, Institute of Medicine and Science for Life Laboratory, Gothenburg University and Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.ORCID 0009-0001-0232-0425
Olle MelanderDepartment of Internal Medicine, Clinical Sciences, Lund University and Skåne University Hospital, Malmö, Sweden.
Margaret Sunitha SelvarajCardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0002-2751-9254
Satoshi KoyamaProgram in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-9286-0360
Rohan BhukarProgram in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Yunfeng RuanProgram in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Johan LjungbergDepartment of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.ORCID 0000-0002-3002-4877
Scott M DamrauerDepartment of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0001-8009-1632
Michael G LevinDivision of Cardiovascular Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID 0000-0002-9937-9932
Andre FrankeInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.ORCID 0000-0003-1530-5811
Klaus BergerInstitute of Epidemiology and Social Medicine, University of Münster, Munster, Germany.
Christian T RuffTIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Giorgio E M MelloniTIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-6371-1334
Frederick K KamanuTIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Kaoru ItoLaboratory for Cardiovascular Genomics and Informatics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.ORCID 0000-0003-1843-773X
Ron DoThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-3144-3627
Ruth J F LoosThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-8532-5087
Heribert SchunkertDepartment of Cardiology, German Heart Centre Munich, TUM University Hospital, School of Medicine and Health, Technical University of Munich, Munich, Germany.ORCID 0000-0001-6428-3001
Quinn S WellsDepartment of Medicine, Division of Cardiology, Vanderbilt University Medical Center, Nashville, TN, USA.
Svati H ShahDuke Molecular Physiology Institute, Duke University, Durham, NC, USA.
Thierry Le TourneauNantes Université, CHU Nantes, CNRS, INSERM, l'institut du Thorax, Nantes, France.ORCID 0000-0002-0110-9054
David Messika-ZeitounDivision of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Christopher GignouxColorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.ORCID 0000-0001-9728-6567
Henning BundgaardDepartment of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.ORCID 0000-0002-0563-7049
Susanna C LarssonMedical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Karl MichaëlssonMedical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Hilma HolmdeCODE genetics/Amgen, Inc., Reykjavik, Iceland.
Anna HelgadottirdeCODE genetics/Amgen, Inc., Reykjavik, Iceland.
Tonu EskoEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
David A van HeelBlizard Institute, Queen Mary University of London, London, UK.ORCID 0000-0002-0637-2265
Patrick MathieuInstitut Universitaire de Cardiologie et de Pneumologie de Québec-Université Laval, Quebec City, Quebec, Canada.ORCID 0000-0002-3805-2004
Nilesh J SamaniDepartment of Cardiovascular Sciences, University of Leicester, Leicester, UK.
J Gustav SmithThe Wallenberg Laboratory/Department of Molecular and Clinical Medicine, Institute of Medicine and Science for Life Laboratory, Gothenburg University and Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.ORCID 0000-0001-6285-9935
Stefan SöderbergDepartment of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.ORCID 0000-0001-9225-1306
Daniel J RaderDivision of Cardiovascular Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Nicholas A MarstonTIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-6164-4617
Marc S SabatineTIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Bogdan PasaniucInterdepartmental Program in Bioinformatics, University of California, Los Angeles, CA, USA.
Kelly ChoDepartment of Medicine, Harvard Medical School, Boston, MA, USA.
Peter W F WilsonAtlanta VA Medical Center, Atlanta, GA, USA.ORCID 0000-0002-5653-7056
Christopher J O'DonnellDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-2667-8624
Kari StefanssondeCODE genetics/Amgen, Inc., Reykjavik, Iceland.ORCID 0000-0003-1676-864X
Yohan BosséInstitut Universitaire de Cardiologie et de Pneumologie de Québec-Université Laval, Quebec City, Quebec, Canada.ORCID 0000-0002-3067-3711
Elena AikawaDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
James C EngertMcGill University Health Centre and Research Institute, Montréal, Quebec, Canada.ORCID 0000-0001-8411-4790
Gina M PelosoDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.ORCID 0000-0002-5355-8636
Pradeep NatarajanCardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. pnatarajan@mgh.harvard.edu.ORCID 0000-0001-8402-7435
George ThanassoulisMcGill University Health Centre and Research Institute, Montréal, Quebec, Canada. g.thanassoulis@gmail.com.ORCID 0000-0002-9930-7189
Funding
Using genetic variation to study biology of blood lipids & coronary heart diseaseR01HL127564 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Pradeep Natarajan, Gina Marie Peloso · 2015 to 2026
$7.3MNHLBI NIH HHS R01 HL127564
Abstract
Aortic stenosis (AS) is a common valvular heart disease and has no pharmacological therapies. We performed a multi-ancestry genome-wide association meta-analysis of 86,864 AS cases among 2,853,408 individuals, discovering 241 autosomal independent risk loci and 3 X chromosome risk loci. We additionally performed sex-stratified and ancestry-stratified genome-wide association studies (GWASs), identifying an additional 5 sex-specific risk loci, 11 risk loci in European ancestry individuals and 1 risk locus in African ancestry individuals. We also performed a transcriptome-wide association study using expression quantitative trait loci from human aortic valves, discovering 54 new genes for which genetically predicted expression influences the risk of AS. We then generated a new polygenic risk score for AS. Finally, we performed gene silencing experiments targeting biologically relevant genes identified by our GWAS. Silencing of CMKLR1 and LTBP4 in human valvular interstitial cells substantially decreased mineralization, implicating a role for polyunsaturated fatty acids and transforming growth factor β signaling in AS.
Indexed as
Aortic Valve StenosisTranscriptomeFemaleGene Expression ProfilingGenetic Predisposition to DiseaseGenome-Wide Association StudyGenomicsHumansMaleMultifactorial InheritancePolymorphism, Single NucleotideQuantitative Trait LociWhite People
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