Evidence map›Paper›PMID 41645906›Full record

SynthesisCirculation2026

Genome and Transcriptome-Wide Analyses Identify Multiple Candidate Genes and a Significant Polygenic Contribution in Bicuspid Aortic Valve.

Sébastien Thériault, Jacob A Holdcraft, Dinara Sharipova, Adèle Faucherre, Radoslaw M Debiec, Gina M Peloso, Baravan Al-Kassou, Sary Aranki, Elena Ashikhmina Swan, Andrea Ballotta and 85 more

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Circulation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Elucidating Gene Functions in Congenital Heart Disease.Current treatment options in cardiovascular medicine · 2026
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

95 authors.

Sébastien Thériault *Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval (S.T., F.D., Z.L., H.D.M., P.P., Y.B., P.M.).ORCID 0000-0003-1893-8307
Jacob A Holdcraft *Department of Biostatistics, School of Public Health, Boston University, MA (J.A.H., G.M.P.).
Dinara Sharipova *Department of Animal Physiology, Institute of Biochemistry and Biology, University of Potsdam, Germany (D.S., S.A.-S.).ORCID 0000-0002-2267-831X
Adèle Faucherre *Institut de Génomique Fonctionnelle, University of Montpellier, Centre national de la recherche scientifique, Institut national de la santé et de la recherche médicale, France (A. Faucherre, C.J.).ORCID 0000-0002-6099-3898
Radoslaw M Debiec *Department of Cardiovascular Sciences, Leicester British Heart Foundation Centre of Research Excellence and National Institute for Health and Care Research Leicester Biomedical Research Centre, University of Leicester (R.M.D., P.S.B., C.P.N., A.P.B., N.J.S., T.R.W.).ORCID 0000-0003-2292-467X
Gina M Peloso *Department of Biostatistics, School of Public Health, Boston University, MA (J.A.H., G.M.P.).ORCID 0000-0002-5355-8636
Baravan Al-KassouDepartment of Medicine II, Heart Center Bonn (B.A.-K., G.N.), University of Bonn and University Hospital Bonn, Germany.ORCID 0000-0003-2967-6613
Sary ArankiBrigham and Women's Hospital, Boston, MA (S.A., M.D.F., S.G.).ORCID 0000-0002-3129-3403
Elena Ashikhmina SwanDepartment of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN (E.A.S.).ORCID 0000-0002-1618-3046
Andrea BallottaCentro Cardiologico Monzino Istituto di Ricovero e Cura a Carattere Scientifico Via Parea, Milan University, Italy (A.B.).
Michele BellinoUniversity Study of Salerno, Italy (M. Bellino).
Hanna M BjörckDivision of Cardiology, Center for Molecular Medicine, Department of Medicine (H.M.B., P.E.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-9155-3609
Anne Sophie BoureauNantes Université, CHU Nantes, Centre national de la recherche scientifique, Institut national de la santé et de la recherche médicale, L'Institut du Thorax, France (A.S.B., F.L., S.L.S., F.S., C.D., T.L.T., J.-J.S.).ORCID 0000-0002-2224-2014
Peter S BraundDepartment of Cardiovascular Sciences, Leicester British Heart Foundation Centre of Research Excellence and National Institute for Health and Care Research Leicester Biomedical Research Centre, University of Leicester (R.M.D., P.S.B., C.P.N., A.P.B., N.J.S., T.R.W.).ORCID 0000-0001-8540-5709
François CorriveauUniversité Laval, Quebec City, Canada (F.C.).
François DagenaisInstitut universitaire de cardiologie et de pneumologie de Québec - Université Laval (S.T., F.D., Z.L., H.D.M., P.P., Y.B., P.M.).
Lasse FolkersenNucleus Genomics, New York, NY (L.F.).ORCID 0000-0003-0708-9530
Amalia ForteUniversity of Campania L. Vanvitelli, Naples, Italy (A. Forte, A.D.C.).
Michael D FranckeBrigham and Women's Hospital, Boston, MA (S.A., M.D.F., S.G.).
Alessandro FrigiolaIstituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, San Donato Milanese, Italy (A. Frigiola, C.d.V., F.P.).
Svetlana GorbatovBrigham and Women's Hospital, Boston, MA (S.A., M.D.F., S.G.).
Dongchuan GuoDepartment of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston (D.G., D.M., D.R.M., S.K.P.).ORCID 0000-0002-7402-3104
Karam M HabchiNew York-Presbyterian Weill Cornell Medical Center, New York, NY (K.M.H.).
Mahyar HeydarpourDepartment of Medicine, Boston, MA (M.H.).ORCID 0000-0002-5741-367X
Eric M IsselbacherMassachusetts General Hospital, Boston (E.M.I., T.S.).ORCID 0000-0003-0393-168X
Chris JoplingInstitut de Génomique Fonctionnelle, University of Montpellier, Centre national de la recherche scientifique, Institut national de la santé et de la recherche médicale, France (A. Faucherre, C.J.).ORCID 0000-0003-0950-0063
Fabien LaporteNantes Université, CHU Nantes, Centre national de la recherche scientifique, Institut national de la santé et de la recherche médicale, L'Institut du Thorax, France (A.S.B., F.L., S.L.S., F.S., C.D., T.L.T., J.-J.S.).ORCID 0000-0003-2509-3293
Solena Le ScouarnecNantes Université, CHU Nantes, Centre national de la recherche scientifique, Institut national de la santé et de la recherche médicale, L'Institut du Thorax, France (A.S.B., F.L., S.L.S., F.S., C.D., T.L.T., J.-J.S.).ORCID 0000-0003-3444-2125
Zhonglin LiInstitut universitaire de cardiologie et de pneumologie de Québec - Université Laval (S.T., F.D., Z.L., H.D.M., P.P., Y.B., P.M.).ORCID 0000-0003-3659-2389
Peter LichtnerHelmholtz Munich, Neuherberg, Germany (P.L., S.W.).ORCID 0000-0001-5981-7996
Carlo MajInstitute of Human Genetics, Philipps University of Marburg, Germany (C.M., J.S.).ORCID 0000-0002-9559-1725
Hasanga D ManikpurageInstitut universitaire de cardiologie et de pneumologie de Québec - Université Laval (S.T., F.D., Z.L., H.D.M., P.P., Y.B., P.M.).ORCID 0000-0002-2365-6956
Christopher P NelsonDepartment of Cardiovascular Sciences, Leicester British Heart Foundation Centre of Research Excellence and National Institute for Health and Care Research Leicester Biomedical Research Centre, University of Leicester (R.M.D., P.S.B., C.P.N., A.P.B., N.J.S., T.R.W.).
Thy B NguyenUniversity of Colorado, Aurora (T.B.N.).ORCID 0000-0002-2354-345X
Russell A NorrisMedical University of South Carolina, Charleston (R.A.N.).ORCID 0000-0001-8462-5726
Chin Siang OngYale University School of Medicine, New Haven, CT (C.S.O.).
Philippe PibarotInstitut universitaire de cardiologie et de pneumologie de Québec - Université Laval (S.T., F.D., Z.L., H.D.M., P.P., Y.B., P.M.).ORCID 0000-0002-3607-279X
Tanmoy RoychowdhuryDepartment of Internal Medicine, Division of Cardiology (T.R., I.S., C.J.W., B.Y.).
Berardo SarubbiDepartment of Biology and Koita Centre for Digital Health, Trivedi School of Biosciences, Ashoka University, Sonepat, India (T.R.).ORCID 0000-0001-9941-8500
Floriane SimonetNantes Université, CHU Nantes, Centre national de la recherche scientifique, Institut national de la santé et de la recherche médicale, L'Institut du Thorax, France (A.S.B., F.L., S.L.S., F.S., C.D., T.L.T., J.-J.S.).ORCID 0000-0002-6366-7211
Thoralf SundtMassachusetts General Hospital, Boston (E.M.I., T.S.).ORCID 0000-0002-0409-7028
Ida SurakkaDepartment of Internal Medicine, Division of Cardiology (T.R., I.S., C.J.W., B.Y.).ORCID 0000-0002-6669-5541
Idit TesslerSheba Medical center, Ramat Gan, Israel (I.T.).ORCID 0000-0002-3297-7022
Cristen J WillerDepartment of Internal Medicine, Division of Cardiology (T.R., I.S., C.J.W., B.Y.).
Susanne WittmannHelmholtz Munich, Neuherberg, Germany (P.L., S.W.).
Bo YangDepartment of Internal Medicine, Division of Cardiology (T.R., I.S., C.J.W., B.Y.).ORCID 0000-0002-2158-9155
Igor BerezovetsDepartment of Cardiac and Thoracic Vascular Surgery, University Heart Center Lübeck, University Medical Center Schleswig-Holstein, Germany (I.B., T.P., S.E.).
Stefanie A DopplerDepartment of Cardiovascular Surgery, Institute Insure (S.A.D., M.D., M.K.), German Heart Center Munich, School of Medicine and Health, Technical University of Munich University Hospital, Technical University of Munich.ORCID 0000-0002-1505-1658
Martina DreßenDepartment of Cardiovascular Surgery, Institute Insure (S.A.D., M.D., M.K.), German Heart Center Munich, School of Medicine and Health, Technical University of Munich University Hospital, Technical University of Munich.ORCID 0000-0003-2200-6254
Katharina KnollDepartment of Cardiovascular Diseases (K.K., H.S., T.T.), German Heart Center Munich, School of Medicine and Health, Technical University of Munich University Hospital, Technical University of Munich.ORCID 0000-0002-2339-591X
Thomas PuehlerDepartment of Cardiac and Thoracic Vascular Surgery, University Heart Center Lübeck, University Medical Center Schleswig-Holstein, Germany (I.B., T.P., S.E.).ORCID 0000-0002-4990-1892
Heribert SchunkertDepartment of Cardiovascular Diseases (K.K., H.S., T.T.), German Heart Center Munich, School of Medicine and Health, Technical University of Munich University Hospital, Technical University of Munich.ORCID 0000-0001-6428-3001
Jean-François AvierinosService de Cardiologie, Assistance Publique - Hôpitaux de Marseille, Hôpital de la Timone, Marseille, France (J.-F.A.).
Malenka M BissellLeeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, United Kingdom (M.M.B.).ORCID 0000-0002-1282-2859
Aidan P BolgerDepartment of Cardiovascular Sciences, Leicester British Heart Foundation Centre of Research Excellence and National Institute for Health and Care Research Leicester Biomedical Research Centre, University of Leicester (R.M.D., P.S.B., C.P.N., A.P.B., N.J.S., T.R.W.).
Yohan BosséInstitut universitaire de cardiologie et de pneumologie de Québec - Université Laval (S.T., F.D., Z.L., H.D.M., P.P., Y.B., P.M.).ORCID 0000-0002-3067-3711
Eduardo BossoneDepartment of Public Health, Faculty of Medicine, University of Naples "Federico II," Italy (E.B.).ORCID 0000-0003-2769-9950
María BrionXenética Cardiovascular, Instituto de Investigación Sanitaria de Santiago, Complexo Hositalario Universitario de Santiago, Santiago de Compostela, Spain (M.B.).ORCID 0000-0001-7463-2148
Rodolfo CitroDepartment of Medicine and Health Science, University of Molise, Campobasso, Italy (R.C.).ORCID 0000-0002-7796-6298
Carlo de VincentiisIstituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, San Donato Milanese, Italy (A. Frigiola, C.d.V., F.P.).ORCID 0000-0002-9945-0057
G Michael DeebDepartment of Cardiac Surgery (G.M.D.).ORCID 0000-0002-4698-2789
Alessandro Della CorteUniversity of Campania L. Vanvitelli, Naples, Italy (A. Forte, A.D.C.).ORCID 0000-0002-4636-3339
Christian DinaNantes Université, CHU Nantes, Centre national de la recherche scientifique, Institut national de la santé et de la recherche médicale, L'Institut du Thorax, France (A.S.B., F.L., S.L.S., F.S., C.D., T.L.T., J.-J.S.).ORCID 0000-0002-7722-7348
Ronen DurstCardiology Department, Hadassah Hebrew University Medical Center, Jerusalem, Israel (R.D., D.G.).ORCID 0000-0003-3559-1050
Stephan EnsmingerDepartment of Cardiac and Thoracic Vascular Surgery, University Heart Center Lübeck, University Medical Center Schleswig-Holstein, Germany (I.B., T.P., S.E.).ORCID 0000-0002-9508-3261
Per ErikssonDivision of Cardiology, Center for Molecular Medicine, Department of Medicine (H.M.B., P.E.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-5635-2692
Arturo EvangelistaHospital Universitari Vall d'Hebron, Barcelona, Spain (A.E.).ORCID 0000-0001-8182-1174
Anders Franco-CerecedaDepartment of Molecular Medicine and Surgery (A.F.-C.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-3427-9455
Dan GilonCardiology Department, Hadassah Hebrew University Medical Center, Jerusalem, Israel (R.D., D.G.).ORCID 0000-0002-7861-1202
Betti GiustiDepartment of Experimental and Clinical Medicine, University of Florence, Italy (B.G., S.N.).ORCID 0000-0002-8708-9444
Simon L HetheringtonKettering General Hospital National Health Service Foundation Trust, Kettering, United Kingdom (S.L.H.).ORCID 0000-0003-1979-451X
Gordon S HugginsTufts Medical Center, Boston, MA (G.S.H.).ORCID 0000-0002-8035-0312
Markus KraneDepartment of Cardiovascular Surgery, Institute Insure (S.A.D., M.D., M.K.), German Heart Center Munich, School of Medicine and Health, Technical University of Munich University Hospital, Technical University of Munich.
Thierry Le TourneauNantes Université, CHU Nantes, Centre national de la recherche scientifique, Institut national de la santé et de la recherche médicale, L'Institut du Thorax, France (A.S.B., F.L., S.L.S., F.S., C.D., T.L.T., J.-J.S.).ORCID 0000-0002-0110-9054
Giuseppe LimongelliDepartment of Translational Medical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy (G.L.).ORCID 0000-0002-8291-9517
Patrick MathieuInstitut universitaire de cardiologie et de pneumologie de Québec - Université Laval (S.T., F.D., Z.L., H.D.M., P.P., Y.B., P.M.).ORCID 0000-0002-3805-2004
David Messika-ZeitounDepartment of Translational Medical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy (G.L.).ORCID 0000-0002-6278-5670
Hector I MichelenaDepartment of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (H.I.M.).ORCID 0000-0002-2341-5247
Dianna MilewiczDepartment of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston (D.G., D.M., D.R.M., S.K.P.).ORCID 0000-0002-7806-0068
Jochen D MuehlschlegelDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (J.D.M.).ORCID 0000-0002-6209-7253
David R MurdockDepartment of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston (D.G., D.M., D.R.M., S.K.P.).ORCID 0000-0002-8536-3091
Georg NickenigDepartment of Medicine II, Heart Center Bonn (B.A.-K., G.N.), University of Bonn and University Hospital Bonn, Germany.ORCID 0000-0003-2944-6033
Stefano NistriDepartment of Experimental and Clinical Medicine, University of Florence, Italy (B.G., S.N.).ORCID 0000-0003-4723-6646
Markus M NöthenInstitute of Human Genetics (M.M.N., J.S.), University of Bonn and University Hospital Bonn, Germany.ORCID 0000-0002-8770-2464
Francesca PluchinottaIstituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, San Donato Milanese, Italy (A. Frigiola, C.d.V., F.P.).
Siddharth K PrakashDepartment of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston (D.G., D.M., D.R.M., S.K.P.).ORCID 0000-0001-6341-9624
Nilesh J SamaniDepartment of Cardiovascular Sciences, Leicester British Heart Foundation Centre of Research Excellence and National Institute for Health and Care Research Leicester Biomedical Research Centre, University of Leicester (R.M.D., P.S.B., C.P.N., A.P.B., N.J.S., T.R.W.).ORCID 0000-0002-3286-8133
Jean-Jacques SchottNantes Université, CHU Nantes, Centre national de la recherche scientifique, Institut national de la santé et de la recherche médicale, L'Institut du Thorax, France (A.S.B., F.L., S.L.S., F.S., C.D., T.L.T., J.-J.S.).ORCID 0000-0002-9578-9475
Tom R WebbDepartment of Cardiovascular Sciences, Leicester British Heart Foundation Centre of Research Excellence and National Institute for Health and Care Research Leicester Biomedical Research Centre, University of Leicester (R.M.D., P.S.B., C.P.N., A.P.B., N.J.S., T.R.W.).ORCID 0000-0001-5998-8226
Stéphane Zaffran *Aix Marseille Université, Institut national de la santé et de la recherche médicale, Marseille Medical Genetics, U1251, France (S.Z.).ORCID 0000-0002-0811-418X
Salim Abdelilah-Seyfried *Department of Animal Physiology, Institute of Biochemistry and Biology, University of Potsdam, Germany (D.S., S.A.-S.).
Kim Eagle *Michigan Medicine, University of Michigan, Ann Arbor (K.E.).ORCID 0000-0003-0031-0191
Johannes Schumacher *Institute of Human Genetics (M.M.N., J.S.), University of Bonn and University Hospital Bonn, Germany.
Teresa Trenkwalder *Department of Cardiovascular Diseases (K.K., H.S., T.T.), German Heart Center Munich, School of Medicine and Health, Technical University of Munich University Hospital, Technical University of Munich.
Simon C Body *Department of Anesthesiology, Boston University, MA (S.C.B.).ORCID 0000-0001-6721-7050

Funding

Cardiac Exosomes in myocardial Ischemic injuryR01HL150401 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI MUEHLSCHLEGEL, JOCHEN DANIEL · 2020 to 2024
$3.3M
Genomics of Post-Operative Atrial Fibrillation After Cardiac SurgeryR01HL149998 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI MUEHLSCHLEGEL, JOCHEN DANIEL, STRANGER, BARBARA E · 2021 to 2024
$3.1M
Genetics of gene expression in human left ventricular myocardiumR01HL118266 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI MUEHLSCHLEGEL, JOCHEN DANIEL · 2013 to 2017
$2.3M
Genetic Etiology of Bicuspid Aortic Valve DiseaseR01HL114823 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI BODY, SIMON C · 2012 to 2016
$2.1M
Genetic Basis of Early Onset Bicuspid Aortic Valve DiseaseR01HL137028 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI PRAKASH, SIDDHARTH KUMAR · 2017 to 2020
$1.5M
Using GenTAC Resources in BioLINCC to discover BAV-specific Aortic PhenotypesR21HL150373 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BODY, SIMON C · 2019 to 2020
$255k
Sex Chromosome Loss and Clonal Hematopoesis in Thoracic Aortic DiseaseR21HL150383 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI PRAKASH, SIDDHARTH KUMAR · 2019 to 2020
$233k
NHLBI NIH HHS R01 HL114823NHLBI NIH HHS R01 HL118266NHLBI NIH HHS R01 HL137028NHLBI NIH HHS R01 HL149998NHLBI NIH HHS R01 HL150401NHLBI NIH HHS R21 HL150373NHLBI NIH HHS R21 HL150383
6 · The paper itself

Abstract

backgroundBicuspid aortic valve (BAV) is a frequent congenital heart defect with a high heritability. Despite this, only a limited number of genes have been associated with the disease, and the molecular mechanisms remain unexplained in most cases. This study aimed to further understand the genetic architecture of BAV.

methodsA genome-wide association study meta-analysis including 9631 cases among 65 677 participants was performed. Genes were prioritized using transcriptomic analyses based on RNA sequencing in relevant tissues, including human fetal and adult aortic valves. The impact of the knockdown or knockout of 4 candidate genes on cardiac development was verified in zebrafish. A polygenic risk score was developed, its association with BAV was evaluated in an independent cohort, and its association with a wide range of phenotypes (n=976) was evaluated in UK Biobank (n=355 618 individuals).

resultsThirty-six genomic loci were identified, including 32 that were not described previously. Among the prioritized genes,

conclusionsThis study supports a significant polygenic contribution to BAV, where the combination of multiple common variants in genes involved in heart morphogenesis disrupts aortic valve development.

Indexed as

Aortic ValveBicuspid Aortic Valve DiseaseGenome-Wide Association StudyMultifactorial InheritanceTranscriptomeAnimalsFemaleGene Expression ProfilingGenetic Risk ScoreHumansMaleZebrafishbicuspid aortic valvegenome-wide association studypolygenic risk scoreRNA sequencingzebrafish

Identifiers

PMID41645906
PMCPMC13001617

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.