SynthesisEuropean heart journal2023
Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis: a genome-wide study.
Open access · hybridAbstract readMeta-Analysis
In one paragraph
Synthesis in European heart journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 2 pooled it
22.8field-weighted citation impact, top 1% of its field
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
60 citing papers in PubMed, 2 syntheses or guidelines pooled it, 104 citations in OpenAlex.
- Genomic and transcriptomic analyses of aortic stenosis enhance therapeutic target discovery and disease prediction.Nature genetics · 2026Pooled it
- Aortic stenosis intricacies beyond the valve: A bidirectional Mendelian randomization study.ESC heart failure · 2025Pooled it
- Low-plastic diet and urinary levels of plastic-associated phthalates and bisphenols: the randomized controlled PERTH Trial.Nature medicine · 2026Trial
- Dyslipidemia Impacts Cardiometabolic Health and CVD Risk in a Relatively Young Otherwise Healthy Population.Journal of clinical hypertension (Greenwich, Conn.) · 2025Trial
- Complement Component C4B Prioritization Through Drug‒Target Mendelian Randomization and Proteomic Analysis Reveals a Novel Therapeutic Target for Calcific Aortic Valve Stenosis.Cardiovascular drugs and therapy · 2026Article
- Epidemiological and bioinformatics analyses of air pollution and genetic susceptibility in aortic stenosis risk.Nature communications · 2026Article
- Article
- Associations of triglyceride-glucose index and hs-CRP with incident aortic valve calcification and mortality in Kailuan study population: a nationwide prospective cohort study.American journal of preventive cardiology · 2026Article
- Association of hematopoietic loss of Y chromosome with valvular heart disease incidence and sex susceptibility.Journal of advanced research · 2026Article
- Specificities of Aortic Stenosis in Women - From Diagnosis to Management.Saudi medical journal · 2026Review
- Inflammatory Prognostic Index: A Novel Predictor of In-Stent Restenosis Following Drug-Eluting Stent-Percutaneous Coronary Intervention.Diagnostics (Basel, Switzerland) · 2026Article
- The role of sortilin in cardiovascular calcification: mechanisms and therapeutic potential.Frontiers in cardiovascular medicine · 2026Review
- 3D immunolabelling of human aortic valves by optimized CUBIC tissue clearing and its application for neural mapping in aortic stenosis.European heart journal open · 2026Article
- Multitrait analyses identify genetic variants associated with aortic valve function and aortic stenosis risk.Nature genetics · 2026Article
- Triglyceride-Glucose Index and the Risk of Calcific Aortic Valve Stenosis: A Bidirectional Mendelian Randomization Study.Anatolian journal of cardiology · 2025Article
- Benefits of Better Cardiovascular Health for Calcific Aortic Valve Stenosis Stratified by Polygenic Risk Score.Genomics, proteomics & bioinformatics · 2025Article
- Diagnostic Pitfalls of Prosthetic Valve Endocarditis: From Sacroiliitis to Coronary Septic Embolization.Diagnostics (Basel, Switzerland) · 2025Article
- A genetic map of human metabolism across the allele frequency spectrum.Nature genetics · 2025Article
- Long-Term Outcomes in Aortic Stenosis: Mortality Analysis in a Selected Patient Group.Journal of personalized medicine · 2025Article
- Lipoprotein (a) in primary cardiovascular disease prevention is actionable today.American heart journal plus : cardiology research and practice · 2025Review
Corrections and comments
- Commented on by
Authors and funding
58 authors at 20 institutions in 7 countries.
Hao Yu ChenDivision of Experimental Medicine, McGill University, 1001 Decarie Blvd., Room EM1.2218, Montreal, Quebec H4A 3J1, Canada.ORCID 0000-0001-8885-7583
Christian DinaNantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, 8 Quai Moncousu, Nantes F-44000, France.ORCID 0000-0002-7722-7348
Aeron M SmallDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
Christian M ShafferVanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University Medical Center, Nashville, USA.
Rebecca T LevinsonVanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University Medical Center, Nashville, USA.
Anna HelgadóttirdeCODE genetics/Amgen Inc., Reykjavik, Iceland.
Romain CapouladeNantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, 8 Quai Moncousu, Nantes F-44000, France.ORCID 0000-0002-7233-7409
Hans Markus MunterMcGill University and Genome Quebec Innovation Centre, Montreal, Canada.ORCID 0000-0002-3165-2840
Andreas MartinssonDepartment of Cardiology, Clinical Sciences, Lund University, Sweden and Skåne University Hospital, Lund, Sweden.ORCID 0000-0003-1461-0777
Benjamin J CairnsMRC Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Linea C TrudsøLaboratory for Molecular Cardiology, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Mary HoekstraDivision of Experimental Medicine, McGill University, 1001 Decarie Blvd., Room EM1.2218, Montreal, Quebec H4A 3J1, Canada.
Hannah A BurrDivision of Experimental Medicine, McGill University, 1001 Decarie Blvd., Room EM1.2218, Montreal, Quebec H4A 3J1, Canada.
Thomas W MarshPreventive and Genomic Cardiology, McGill University Health Centre and Research Institute, 1001 Decarie Blvd., Room D05.5120, Montreal, Quebec H4A 3J1, Canada.
Scott M DamrauerDepartment of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
Line DufresnePreventive and Genomic Cardiology, McGill University Health Centre and Research Institute, 1001 Decarie Blvd., Room D05.5120, Montreal, Quebec H4A 3J1, Canada.
Solena Le ScouarnecNantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, 8 Quai Moncousu, Nantes F-44000, France.
David Messika-ZeitounDepartment of Cardiology, Assistance Publique - Hôpitaux de Paris, Bichat Hospital, Paris, France.ORCID 0000-0002-6278-5670
Dilrini K RanatungaDivision of Research, Kaiser Permanente of Northern California, Oakland, USA.
Rachel A WhitmerDepartment of Public Health Sciences, University of California Davis, Davis, USA.
Amélie BonnefondUniversity Lille, Inserm, CNRS, CHU Lille, Institut Pasteur de Lille, UMR1283-8199 EGID, Lille, France.
Garðar SveinbjornssondeCODE genetics/Amgen Inc., Reykjavik, Iceland.
Ragnar DaníelsenInternal Medicine and Emergency Services, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland.
David O ArnardeCODE genetics/Amgen Inc., Reykjavik, Iceland.ORCID 0000-0002-9442-1644
Gudmundur ThorgeirssondeCODE genetics/Amgen Inc., Reykjavik, Iceland.ORCID 0000-0002-7146-1395
Unnur ThorsteinsdottirdeCODE genetics/Amgen Inc., Reykjavik, Iceland.ORCID 0000-0002-7049-2827
Daníel F GudbjartssondeCODE genetics/Amgen Inc., Reykjavik, Iceland.
Hilma HólmdeCODE genetics/Amgen Inc., Reykjavik, Iceland.
Jonas GhouseLaboratory for Molecular Cardiology, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Morten Salling OlesenLaboratory for Molecular Cardiology, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Alex H ChristensenLaboratory for Molecular Cardiology, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Susan MikkelsenDepartment of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark.
Rikke Louise JacobsenDepartment of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Joseph DowsettDepartment of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Ole Birger Vesterager PedersenDepartment of Clinical Immunology, Zealand University Hospital, Naestved, Denmark.
Christian ErikstrupDepartment of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark.ORCID 0000-0001-6551-6647
Sisse R OstrowskiDepartment of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Regeneron Genetics Center
Christopher J O'DonnellNational Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Boston, USA.
Matthew J BudoffThe Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, USA.
Vilmundur GudnasonFaculty of Medicine, University of Iceland, Reykjavík, Iceland.
Wendy S PostDivision of Cardiology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, USA.
Jerome I RotterThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, USA.
Mark LathropMcGill University and Genome Quebec Innovation Centre, Montreal, Canada.
Henning BundgaardDepartment of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.ORCID 0000-0002-0563-7049
Bengt JohanssonDepartment of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.ORCID 0000-0003-0976-6910
Johan LjungbergDepartment of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
Ulf NäslundDepartment of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.ORCID 0000-0003-4100-8298
Thierry Le TourneauNantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, 8 Quai Moncousu, Nantes F-44000, France.
J Gustav SmithDepartment of Cardiology, Clinical Sciences, Lund University, Sweden and Skåne University Hospital, Lund, Sweden.
Quinn S WellsVanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University Medical Center, Nashville, USA.
Stefan SöderbergDepartment of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
Kári StefánssondeCODE genetics/Amgen Inc., Reykjavik, Iceland.
Jean-Jacques SchottNantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, 8 Quai Moncousu, Nantes F-44000, France.
Daniel J RaderDepartments of Genetics and Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
Robert ClarkeMRC Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
James C EngertDivision of Experimental Medicine, McGill University, 1001 Decarie Blvd., Room EM1.2218, Montreal, Quebec H4A 3J1, Canada.ORCID 0000-0001-8411-4790
George ThanassoulisDivision of Experimental Medicine, McGill University, 1001 Decarie Blvd., Room EM1.2218, Montreal, Quebec H4A 3J1, Canada.
deCODE Genetics (Iceland) · ISCopenhagen University Hospital · DKMcGill University Health Centre · CACentre National de la Recherche Scientifique · FRUmeå University · SEUniversity of Pennsylvania · USVanderbilt University Medical Center · USMcGill University and Génome Québec Innovation Centre · CAUCLA Medical Center · USUniversity of Oxford · GBAarhus University · DKAarhus University Hospital · DKJohns Hopkins University · USKaiser Permanente · USLund University · SENational Heart Lung and Blood Institute · USNational University Hospital of Iceland · ISSahlgrenska University Hospital · SEUniversity of California, Davis · USUniversity of Copenhagen · DK
Funding
Vanderbilt Institute for Clinical and Translational Research (VICTR) -Identifying correlates of functional immunity in SARS-CoV-2 convalescent plasmaUL1TR002243 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Paul A. Harris, Wesley H Self · 2017 to 2026
$130.7MUCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1MInstitute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1MVANDERBILT UNIVERSITY CTSA FOR PEDIATRIC RESEARCHUL1RR024975 · NCRR · VANDERBILT UNIVERSITY · PI BERNARD, GORDON RAPHAEL · 2007 to 2011
$45.7MThe Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MILES Frome WILKINSON · 2003 to 2026
$40.4MWake Forest Clinical and Translational Science AwardUL1TR001420 · NCATS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ARD, JAMY D, FOLEY, KRISTIE L · 2015 to 2023
$32.3MClinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2MUC Davis Alzheimer's Disease Research CenterP30AG072972 · NIA · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Charles DeCarli, Rachel A Whitmer · 2021 to 2026
$25.2MPharmacogenomics of Arrhythmia TherapyU19HL065962 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RODEN, DAN M · 2010 to 2014
$17.4MTask Area A Core Study Operations.Task Area A shall encompass annual follow-up of cohort members, clinical endpoints ascertainment, study coordination activities, maintenance of the database and biosp75N92020D00001 · NHLBI · UNIVERSITY OF WASHINGTON · PI MCCLELLAND, ROBYN LEAGH · 2020 to 2025
$17.2MUnderstanding and preventing HLA-associated drug reactionsP50GM115305 · NIGMS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PHILLIPS, ELIZABETH, RODEN, DAN M · 2015 to 2019
$13.0MBritish Heart Foundation RE/18/3/34214CSRD VA IK2 CX001780NCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR000445NCATS NIH HHS UL1 TR001079NCATS NIH HHS UL1 TR001420NCATS NIH HHS UL1 TR001881NCATS NIH HHS UL1 TR002243NCRR NIH HHS S10 RR025141NCRR NIH HHS UL1 RR024975NHGRI NIH HHS U01 HG004798NHGRI NIH HHS U01 HG006378NHLBI NIH HHS 75N92020D00001NHLBI NIH HHS 75N92020D00002NHLBI NIH HHS 75N92020D00003NHLBI NIH HHS 75N92020D00004NHLBI NIH HHS 75N92020D00005NHLBI NIH HHS 75N92020D00006NHLBI NIH HHS 75N92020D00007NHLBI NIH HHS HHSN268201500003CNHLBI NIH HHS HHSN268201500003INHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS N01 HC095169NHLBI NIH HHS R01 HL071739NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL128550NHLBI NIH HHS R01 HL146860NHLBI NIH HHS U19 HL065962NIA NIH HHS P30 AG072972NICHD NIH HHS R01 HD074711NIDDK NIH HHS P30 DK063491NIGMS NIH HHS P50 GM115305NIGMS NIH HHS RC2 GM092618NINDS NIH HHS R01 NS032830
Abstract
aimsAlthough highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS. METHODS AND
resultsA genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10-8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2-SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26-1.35; P = 2.7 × 10-51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08-1.37; P = 1.4 × 10-3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90-5.12; P = 2.1 × 10-20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17-1.23; P = 4.8 × 10-73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05-1.9; P = 1.9 × 10-12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS.
conclusionDyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies.
Indexed as
Aortic Valve StenosisDyslipidemiasAdiposityApolipoproteinsGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansInflammationMendelian Randomization AnalysisObesityPolymorphism, Single NucleotideRisk FactorsApolipoproteinsAortic stenosisGene expressionGenetic risk scoreGenome-wide association studyMendelian randomizationPhenome-wide association study
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