SynthesisThe Lancet. Respiratory medicine2019
Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis.
Open access · hybridAbstract readMeta-Analysis
In one paragraph
Synthesis in The Lancet. Respiratory medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers, 5 of them syntheses that pooled it.
0numbers the graph read from it
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145citing papers in PubMed, 5 pooled it
10.6field-weighted citation impact, top 1% of its field
What it found
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Who cites it
145 citing papers in PubMed, 5 syntheses or guidelines pooled it, 203 citations in OpenAlex.
- Multi-ancestry investigation of the genomics of erectile dysfunction.Nature communications · 2025Pooled it
- Genetically determined gut microbiota associates with pulmonary arterial hypertension: a Mendelian randomization study.BMC pulmonary medicine · 2024Pooled it
- Allele-specific control of rodent and human lncRNA KMT2E-AS1 promotes hypoxic endothelial pathology in pulmonary hypertension.Science translational medicine · 2024Pooled it
- Differential expression of members of SOX family of transcription factors in failing human hearts.Translational research : the journal of laboratory and clinical medicine · 2022Pooled it
- Pooled it
- Proteogenomic Profiling of Idiopathic Pulmonary Arterial Hypertension Identifies Sex-Differential Proteins and Candidate Therapeutic Targets.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Genetic variants in pulmonary hypertension associated with chronic obstructive pulmonary disease.Current opinion in pulmonary medicine · 2026Review
- ImpairedERJ open research · 2026Article
- Artificial Intelligence and Multi-Omics Approaches in the Precision Management of Pulmonary Hypertension: From Early Diagnosis to Therapeutic Stratification.International journal of molecular sciences · 2026Review
- Variation inCirculation research · 2026Article
- Genetic Determinants of Pulmonary Artery Size in over 50,000 Subjects with and without COPD.medRxiv : the preprint server for health sciences · 2026Article
- Sickle cell disease-associated pulmonary hypertension: an integrated framework linking pathologies, mechanisms, and clinical phenotypes.EBioMedicine · 2026Review
- Molecular-Genetic Basis of Pulmonary Arterial Hypertension (PAH).Current issues in molecular biology · 2026Review
- Identification of drug candidates for rescue of SOX17 gene targets in pulmonary arterial hypertension.bioRxiv : the preprint server for biology · 2026Article
- Pulmonary Vascular Signaling in Pulmonary Hypertension: Potential Role of Endothelial CaArteriosclerosis, thrombosis, and vascular biology · 2026Review
- The Role of Genetics in Congenital Heart Disease-Associated Pulmonary Arterial Hypertension.Pediatric cardiology · 2026Observational
- The Potential Role of Calcium Channels in Pulmonary Hypertension.BioMed research international · 2026Review
- Article
- Improving polygenic risk prediction performance by integrating electronic health records through phenotype embedding.American journal of human genetics · 2025Article
- SOX17-silenced HPAECs upregulate NF-κB-induced CXCL10 and CXCL11: implications for lymphocyte chemotaxis in SOX17-PAH.Scientific reports · 2025Article
85 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
121 authors at 20 institutions in 8 countries.
Christopher J RhodesDepartment of Medicine, Imperial College London, London, UK.
Ken BataiDepartment of Surgery, University of Arizona, Tucson, AZ, USA.
Marta BledaDepartment of Medicine, University of Cambridge, Cambridge, UK.
Matthias HaimelDepartment of Medicine, University of Cambridge, Cambridge, UK.
Laura SouthgateMolecular and Clinical Sciences Research Institute, St George's University of London, London, UK.
Marine GermainSorbonne Universités, UPMC, INSERM, Paris, France.
Michael W PauciuloHuman Genetics, Cincinnati, OH, USA.
Charaka HadinnapolaDepartment of Medicine, University of Cambridge, Cambridge, UK.
Jurjan AmanDepartment of Medicine, Imperial College London, London, UK.
Barbara GirerdUniversity Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, Paris, France.
Amit AroraDepartment of Surgery, University of Arizona, Tucson, AZ, USA.
Jo KnightData Science Institute, Lancaster University, Lancaster, UK.
Ken B HanscombeGenetics and Molecular Medicine, King's College London, London, UK.
Jason H KarnesPharmacy Practice and Science, University of Arizona, Tucson, AZ, USA.
Marika KaakinenDepartment of Medicine, Imperial College London, London, UK.
Henning GallUniversity of Giessen and Marburg Lung Center, Giessen, Germany.
Anna UlrichDepartment of Medicine, Imperial College London, London, UK.
Lars HarbaumDepartment of Medicine, Imperial College London, London, UK.
Inês CebolaDepartment of Medicine, Imperial College London, London, UK.
Jorge FerrerDepartment of Medicine, Imperial College London, London, UK.
Katie LutzHuman Genetics, Cincinnati, OH, USA.
Emilia M SwietlikDepartment of Medicine, University of Cambridge, Cambridge, UK.
Ferhaan AhmadUniversity of Iowa, Iowa City, IA, USA.
Philippe AmouyelUniversity of Lille, Lille, France.
Stephen L ArcherQueen's University, Kingston, ON, Canada.
Rahul ArgulaMedical University of South Carolina, Charleston, SC, USA.
Eric D AustinVanderbilt University, Nashville, TN, USA.
David BadeschUniversity of Colorado Denver, Denver, CO, USA.
Sahil BakshiBaylor Research Institute, Plano, TX, USA.
Christopher BarnettMedstar Health, Washington, DC, USA.
Raymond BenzaAllegheny-Singer Research Institute, Pittsburgh, PA, USA.
Nitin BhattOhio State University, Columbus, OH, USA.
Harm J BogaardVU University Medical Center, Amsterdam, Netherlands.
Charles D BurgerMayo Clinic Florida, Jacksonville, FL, USA.
Murali ChakinalaWashington University, St Louis, MO, USA.
Colin ChurchGolden Jubilee National Hospital, Glasgow, UK.
John G CoghlanRoyal Free Hospital, London, UK.
Robin CondliffeRoyal Hallamshire Hospital, Sheffield, UK.
Paul A CorrisUniversity of Newcastle, Newcastle, UK.
Cesare DanesinoUniversity of Pavia, Pavia, Italy.
Stéphanie DebetteUniversity of Bordeaux, Bordeaux, France.
C Gregory ElliottIntermountain Medical Center, Murray, UT, USA.
Jean ElwingUniversity of Cincinnati, Cincinnati OH, USA.
Melanie EyriesSorbonne Universités, UPMC, INSERM, Paris, France.
Terry FortinDuke University Medical Center, Durham, NC, USA; University of Kiel, Kiel, Germany.
Andre FrankeUniversity of Kiel, Kiel, Germany.
Robert P FrantzMayo Clinic, Rochester, MN, USA.
Adaani FrostHouston Methodist Research Institute, Houston, TX, USA.
Joe G N GarciaDepartment of Medicine, University of Arizona, Tucson, AZ, USA.
Stefano GhioFondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Hossein-Ardeschir GhofraniUniversity of Giessen and Marburg Lung Center, Giessen, Germany.
J Simon R GibbsNational Heart and Lung Institute, Imperial College London, London, UK.
John HarleyCAGE, Cincinnati, OH, USA.
Hua HeHuman Genetics, Cincinnati, OH, USA.
Nicholas S HillTufts-New England Medical Center, Boston, MA, USA.
Russel HirschCincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; University of Cincinnati, Cincinnati OH, USA.
Arjan C HouwelingVU University Medical Center, Amsterdam, Netherlands.
Luke S HowardNational Heart and Lung Institute, Imperial College London, London, UK.
Dunbar IvyHealth Sciences Center, University of Colorado, Aurora, CO, USA.
David G KielyRoyal Hallamshire Hospital, Sheffield, UK.
James KlingerRhode Island Hospital, Providence, RI, USA.
Gabor KovacsLudwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.
Tim LahmIndiana University, Indianapolis, IN, USA.
Matthias LaudesUniversity of Kiel, Kiel, Germany.
Rajiv D MachadoUniversity of Lincoln, Lincoln, UK.
Robert V MacKenzie RossRoyal United Hospitals Bath NHS Foundation Trust, Bath, UK.
Keith MarsoloBiomedical Informatics, Cincinnati, OH, USA.
Lisa J MartinHuman Genetics, Cincinnati, OH, USA.
Shahin MoledinaGreat Ormond Street Hospital, London, UK.
David MontaniUniversity Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, Paris, France.
Steven D NathanInova Heart and Vascular Institute, Falls Church, VA, USA.
Michael NewnhamDepartment of Medicine, University of Cambridge, Cambridge, UK; Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria; Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.
Andrea OlschewskiLudwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.
Horst OlschewskiLudwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.
Ronald J OudizHarbor-UCLA Medical Center, Torrance, CA, USA.
Willem H OuwehandDepartment of Haematology, University of Cambridge, Cambridge, UK.
Andrew J PeacockGolden Jubilee National Hospital, Glasgow, UK.
Joanna Pepke-ZabaPapworth Hospital, Papworth, UK.
Zia RehmanEast Carolina University, Greenville, NC, USA.
Ivan RobbinsVanderbilt University School of Medicine, Nashville, TN, USA.
Dan M RodenVanderbilt University School of Medicine, Nashville, TN, USA.
Erika B RosenzweigColumbia University, New York, NY, USA.
Ghulam SaydainWayne State University, Detroit, MI, USA.
Laura ScelsiFondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Robert SchilzUniversity Hospital of Cleveland, Cleveland, OH, USA.
Werner SeegerUniversity of Giessen and Marburg Lung Center, Giessen, Germany.
Christian M ShafferVanderbilt University School of Medicine, Nashville, TN, USA.
Robert W SimmsBoston University School of Medicine, Boston, MA, USA.
Marc SimonUniversity of Pittsburgh, Pittsburgh, PA, USA.
Olivier SitbonUniversity Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, Paris, France.
Jay SuntharalingamRoyal United Hospitals Bath NHS Foundation Trust, Bath, UK.
Haiyang TangDepartment of Medicine, University of Arizona, Tucson, AZ, USA.
Alexander Y TchourbanovAmbry Genetics, Aliso Viejo, CA, USA.
Thenappan ThenappanUniversity of Minnesota, Minneapolis, MN, USA.
Fernando TorresUniversity of Texas Southwestern Medical Center, Dallas, TX, USA.
Mark R ToshnerDepartment of Medicine, University of Cambridge, Cambridge, UK.
Carmen M TreacyDepartment of Medicine, University of Cambridge, Cambridge, UK.
Anton Vonk NoordegraafVU University Medical Center, Amsterdam, Netherlands.
Quinten WaisfiszVU University Medical Center, Amsterdam, Netherlands.
Anna K WalsworthHuman Genetics, Cincinnati, OH, USA.
Robert E WalterLouisiana State University Health, Shreveport, LA, USA.
John WhartonDepartment of Medicine, Imperial College London, London, UK.
R James WhiteUniversity of Rochester Medical Center, Rochester, NY, USA.
Jeffrey WiltSpectrum Health Hospitals, Grand Rapids, MI, USA.
Stephen J WortNational Heart and Lung Institute, Imperial College London, London, UK.
Delphine YungSeattle Children's Hospital, Seattle, WA, USA.
Allan LawrieUniversity of Sheffield, Sheffield, UK.
Marc HumbertUniversity Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, Paris, France.
Florent SoubrierSorbonne Universités, UPMC, INSERM, Paris, France.
David-Alexandre TrégouëtSorbonne Universités, UPMC, INSERM, Paris, France.
Inga ProkopenkoDepartment of Medicine, Imperial College London, London, UK.
Richard KittlesCity of Hope, Duarte, CA, USA.
Stefan GräfDepartment of Medicine, University of Cambridge, Cambridge, UK.
William C NicholsHuman Genetics, Cincinnati, OH, USA.
Richard C TrembathGenetics and Molecular Medicine, King's College London, London, UK.
Ankit A DesaiIndiana University, Indianapolis, IN, USA. Electronic address: ankdesai@iu.edu.
Nicholas W MorrellDepartment of Medicine, University of Cambridge, Cambridge, UK. Electronic address: nwm23@cam.ac.uk.
Martin R WilkinsDepartment of Medicine, Imperial College London, London, UK. Electronic address: m.wilkins@imperial.ac.uk.
UK NIHR BioResource Rare Diseases Consortium
UK PAH Cohort Study Consortium
US PAH Biobank Consortium
Imperial College London · GBUniversity of Cambridge · GBCenter for Human Genetics · USUniversity of Arizona · USAmsterdam UMC Location VUmc · NLUniversité Paris-Saclay · FRVanderbilt University · USInserm · FRLudwig Boltzmann Institute for Lung Vascular Research · ATGolden Jubilee National Hospital · GBIndiana University – Purdue University Indianapolis · USKiel University · DEKing's College London · GBRoyal Hallamshire Hospital · GBRoyal United Hospital Bath NHS Trust · GBUniversities of Giessen and Marburg Lung Center · DEUniversity of Cincinnati · USAlaska Heart and Vascular Institute · USAllegheny-Singer Research Institute · USAmbry Genetics (United States) · US
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
$130.7MVANDERBILT 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
$41.4MNational Biological Sample and Data Repository for PAHR24HL105333 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI NICHOLS, WILLIAM C · 2012 to 2016
$10.1MVESPA: Vanderbilt Electronic Systems for Pharmacogenomic AssessmentRC2GM092618 · NIGMS · VANDERBILT UNIVERSITY · PI DENNY, JOSHUA C., RODEN, DAN M · 2009 to 2010
$6.4MBetter Outcomes for Children: Promoting Excellence in Healthcare Genomics to Inform PolicyU01HG008666 · NHGRI · CINCINNATI CHILDRENS HOSP MED CTR · PI HARLEY, JOHN BARKER · 2015 to 2019
$4.2MNovel Involvement of NAMPT and TLR4 in PAH Vascular RemodelingR01HL141387 · NHLBI · UNIVERSITY OF FLORIDA · PI Joe G. N. Garcia, Ayako Makino · 2019 to 2026
$3.8MPathogenic Role of IL-18 in Sickle Cell Cardiomyopathy and Inducible Ventricular TachycardiaR01HL136603 · NHLBI · UNIVERSITY OF ARIZONA · PI DESAI, ANKIT A · 2017 to 2021
$2.4MAutomated Storage and Retrieval of Biological SystemsS10RR025141 · NCRR · VANDERBILT UNIVERSITY · PI RODEN, DAN M · 2008 to 2008
$988kBritish Heart Foundation FS/13/48/30453British Heart Foundation FS/15/59/31839British Heart Foundation PG/11/116/29288British Heart Foundation SP/12/12/29836Medical Research Council MC_UP_1102/20Medical Research Council MR/J011711/1Medical Research Council MR/K020919/1Medical Research Council MR/L02036X/1NCATS NIH HHS UL1 TR000445NCATS NIH HHS UL1 TR002243NCRR NIH HHS S10 RR025141NCRR NIH HHS UL1 RR024975NHGRI NIH HHS U01 HG008666NHLBI NIH HHS R01 HL136603NHLBI NIH HHS R01 HL141387NHLBI NIH HHS R24 HL105333NIGMS NIH HHS RC2 GM092618Wellcome Trust
Abstract
backgroundRare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes.
methodsWe did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension. These GWAS used data from four international case-control studies across 11 744 individuals with European ancestry (including 2085 patients). One GWAS used genotypes from 5895 whole-genome sequences and the other GWAS used genotyping array data from an additional 5849 individuals. Cross-validation of loci reaching genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and tested associations with duration of survival. All-cause mortality was the primary endpoint in survival analyses.
findingsA locus near SOX17 (rs10103692, odds ratio 1·80 [95% CI 1·55-2·08], p=5·13 × 10
interpretationThis is the first study to report that common genetic variation at loci in an enhancer near SOX17 and in HLA-DPA1/DPB1 is associated with pulmonary arterial hypertension. Impairment of SOX17 function might be more common in pulmonary arterial hypertension than suggested by rare mutations in SOX17. Further studies are needed to confirm the association between HLA typing or rs2856830 genotyping and survival, and to determine whether HLA typing or rs2856830 genotyping improves risk stratification in clinical practice or trials.
fundingUK NIHR, BHF, UK MRC, Dinosaur Trust, NIH/NHLBI, ERS, EMBO, Wellcome Trust, EU, AHA, ACClinPharm, Netherlands CVRI, Dutch Heart Foundation, Dutch Federation of UMC, Netherlands OHRD and RNAS, German DFG, German BMBF, APH Paris, INSERM, Université Paris-Sud, and French ANR.
Indexed as
Pulmonary Arterial HypertensionFemaleGenetic Predisposition to DiseaseGenetic VariationGenome-Wide Association StudyGenotyping TechniquesHLA-DP alpha-ChainsHLA-DP beta-ChainsHumansMaleMiddle AgedPolymorphism, Single NucleotideRisk AssessmentSignal TransductionSOXF Transcription FactorsSurvival AnalysisHLA-DPA1 antigenHLA-DP alpha-ChainsHLA-DPB1 antigenHLA-DP beta-ChainsSOX17 protein, humanSOXF Transcription Factors
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