Evidence mapPaperPMID 40038546Full record

SynthesisNature genetics2025

Genome-wide association study meta-analysis provides insights into the etiology of heart failure and its subtypes.

Albert Henry, Xiaodong Mo, Chris Finan, Mark D Chaffin, Doug Speed, Hanane Issa, Spiros Denaxas, James S Ware, Sean L Zheng, Anders Malarstig and 175 more

Abstract readMeta-Analysis
In one paragraph

Synthesis in Nature genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
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

29 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Observational
  6. Review
  7. Article
  8. Article
  9. Exploration of the Pathogenesis and Treatment of Heart Failure.Reviews in cardiovascular medicine · 2026
    Review
  10. Observational
  11. Genetic factors contributing to atherosclerosis.Current opinion in cardiology · 2026
    Review
  12. Article
  13. Review
  14. Article
  15. Observational
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

185 authors.

Albert HenryInstitute of Cardiovascular Science, University College London, London, UK.ORCID http://orcid.org/0000-0001-7422-2288
Xiaodong MoInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
Chris FinanInstitute of Cardiovascular Science, University College London, London, UK.ORCID http://orcid.org/0000-0002-3319-1937
Mark D ChaffinProgram in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-1234-5562
Doug SpeedCenter for Quantitative Genetics and Genomics, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0000-0002-0096-9765
Hanane IssaInstitute of Health Informatics, University College London, London, UK.
Spiros DenaxasInstitute of Health Informatics, University College London, London, UK.
James S WareProgram in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-6110-5880
Sean L ZhengNational Heart & Lung Institute, Imperial College London, London, UK.ORCID http://orcid.org/0000-0002-5762-6392
Anders MalarstigCardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
Jasmine GrattonInstitute of Cardiovascular Science, University College London, London, UK.
Isabelle BondInstitute of Cardiovascular Science, University College London, London, UK.
Carolina RoselliProgram in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-5267-6756
David MillerDivision of Biosciences, University College London, London, UK.
Sandesh ChopadeInstitute of Cardiovascular Science, University College London, London, UK.
A Floriaan SchmidtInstitute of Cardiovascular Science, University College London, London, UK.ORCID http://orcid.org/0000-0003-1327-0424
Erik AbnerEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.ORCID http://orcid.org/0000-0002-6529-3161
Lance AdamsGeisinger Health System, Danville, PA, USA.
Charlotte AnderssonDepartment of Cardiology, Herlev Gentofte Hospital, Herlev, Denmark.
Krishna G AragamProgram in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-3223-9131
Johan ÄrnlövDepartment of Neurobiology, Care Sciences and Society/Section of Family Medicine and Primary Care, Karolinska Institutet, Stockholm, Sweden.
Geraldine AsselinMontreal Heart Institute, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0002-3702-2962
Anna Axelsson RajaDepartment of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Joshua D BackmanAnalytical Genetics, Regeneron Genetics Center, Tarrytown, NY, USA.ORCID http://orcid.org/0000-0001-7262-0880
Traci M BartzDepartment of Biostatistics, University of Washington, Seattle, WA, USA.
Kiran J BiddingerProgram in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Mary L BiggsDepartment of Biostatistics, University of Washington, Seattle, WA, USA.
Heather L BloomDepartment of Medicine, Division of Cardiology, Emory University Medical Center, Atlanta, GA, USA.
Eric BoersmaDepartment of Cardiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Jeffrey BrandimartoPenn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Michael R BrownDepartment of Epidemiology, Human Genetics, and Environmental Sciences, The University of Texas School of Public Health, Houston, TX, USA.ORCID http://orcid.org/0000-0002-5235-9037
Søren BrunakNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0003-0316-5866
Mie Topholm BruunDepartment of Clinical Immunology, Odense University Hospital, Odense, Denmark.ORCID http://orcid.org/0000-0002-8819-5388
Leonard BuckbinderPfizer Worldwide Research & Development, Cambridge, MA, USA.
Henning BundgaardDepartment of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
David J CareyDepartment of Molecular and Functional Genomics, Geisinger, Danville, PA, USA.
Daniel I ChasmanDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Xing ChenPfizer Worldwide Research & Development, Cambridge, MA, USA.
James P CookDepartment of Biostatistics, University of Liverpool, Liverpool, UK.
Tomasz CzubaDepartment of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg University and Sahlgrenska University Hospital, Gothenburg, Sweden.
Simon de DenusMontreal Heart Institute, Montreal, Quebec, Canada.
Abbas DehghanMRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, Imperial College London, London, UK.ORCID http://orcid.org/0000-0001-6403-016X
Graciela E DelgadoVth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Heidelberg, Germany.
Alexander S DoneyDivision of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
Marcus DörrDepartment of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0001-7471-475X
Joseph DowsettDepartment of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.ORCID http://orcid.org/0000-0001-5381-2633
Samuel C DudleyDepartment of Medicine, Cardiovascular Division, University of Minnesota, Minneapolis, MN, USA.ORCID http://orcid.org/0000-0001-5843-5961
Gunnar EngströmDepartment of Clinical Sciences, Lund University, Malmö, Sweden.
Christian ErikstrupDepartment of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark.ORCID http://orcid.org/0000-0001-6551-6647
Tõnu EskoProgram in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Eric H Farber-EgerVanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0003-0281-3796
Stephan B FelixDepartment of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.
Sarah FinerCentre for Primary Care and Public Health, Wolfson Institute of Population Health, Queen Mary University of London, London, UK.ORCID http://orcid.org/0000-0002-2684-4653
Ian FordRobertson Center for Biostatistics, Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.ORCID http://orcid.org/0000-0001-5927-1823
Mohsen GhanbariDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.ORCID http://orcid.org/0000-0002-9476-7143
Sahar GhasemiDZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany.
Jonas GhouseDepartment of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Vilmantas GiedraitisDepartment of Public Health and Caring Sciences, Geriatrics, Uppsala, Sweden.ORCID http://orcid.org/0000-0003-3423-2021
Franco GiulianiniDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
John S GottdienerDepartment of Medicine, Division of Cardiology, University of Maryland School of Medicine, Baltimore, MD, USA.
Stefan GrossDepartment of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0003-4121-7161
Daníel F GuðbjartssondeCODE genetics/Amgen Inc., Reykjavik, Iceland.ORCID http://orcid.org/0000-0002-5222-9857
Hongsheng GuiCenter for Individualized and Genomic Medicine Research, Department of Internal Medicine, Henry Ford Hospital, Detroit, MI, USA.ORCID http://orcid.org/0000-0002-0460-7446
Rebecca GutmannDivision of Cardiovascular Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
Sara HäggDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-2452-1500
Christopher M HaggertyDepartment of Molecular and Functional Genomics, Geisinger, Danville, PA, USA.
Åsa K HedmanCardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.ORCID http://orcid.org/0000-0001-5413-204X
Anna HelgadottirdeCODE genetics/Amgen Inc., Reykjavik, Iceland.ORCID http://orcid.org/0000-0002-1806-2467
Harry HemingwayInstitute of Health Informatics, University College London, London, UK.ORCID http://orcid.org/0000-0003-2279-0624
Hans HillegeDepartment of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Craig L HydePfizer Worldwide Research & Development, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-6939-287X
Bitten Aagaard JensenDepartment of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark.ORCID http://orcid.org/0000-0001-8306-1332
J Wouter JukemaDepartment of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.ORCID http://orcid.org/0000-0002-3246-8359
Isabella KardysDepartment of Cardiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Ravi KarraDepartment of Medicine, Division of Cardiology, Duke University Medical Center, Durham, NC, USA.ORCID http://orcid.org/0000-0001-6741-285X
Maryam KavousiDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.ORCID http://orcid.org/0000-0001-5976-6519
Jorge R KizerCardiology Section, San Francisco Veterans Affairs Health System, and Departments of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
Marcus E KleberVth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Heidelberg, Germany.ORCID http://orcid.org/0000-0003-0663-7275
Lars KøberDepartment of Cardiology, Nordsjaellands Hospital, Copenhagen, Denmark.
Andrea KoekemoerDepartment of Cardiovascular Sciences, University of Leicester and NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.ORCID http://orcid.org/0000-0001-8222-3547
Karoline KuchenbaeckerDivision of Psychiatry, University College London, London, UK.ORCID http://orcid.org/0000-0001-9726-603X
Yi-Pin LaiPfizer Worldwide Research & Development, Cambridge, MA, USA.
David LanfearCenter for Individualized and Genomic Medicine Research, Department of Internal Medicine, Henry Ford Hospital, Detroit, MI, USA.
Claudia LangenbergPrecision Healthcare University Research Institute, Queen Mary University of London, London, UK.ORCID http://orcid.org/0000-0002-5017-7344
Honghuang LinNational Heart, Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, USA.ORCID http://orcid.org/0000-0003-3043-3942
Lars LindDepartment of Medical Sciences, Uppsala University, Uppsala, Sweden.
Cecilia M LindgrenProgram in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Peter P LiuUniversity of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Barry LondonDivision of Cardiovascular Medicine and Abboud Cardiovascular Research Center, University of Iowa, Iowa City, IA, USA.
Brandon D LoweryVanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0003-0898-6137
Jian'an LuanMRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0003-3137-6337
Steven A LubitzProgram in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-9599-4866
Patrik MagnussonDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-7315-7899
Kenneth B MarguliesPenn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Nicholas A MarstonTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-6164-4617
Hilary MartinWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.ORCID http://orcid.org/0000-0002-4454-9084
Winfried MärzVth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Heidelberg, Germany.
Olle MelanderDepartment of Internal Medicine, Clinical Sciences, Lund University and Skåne University Hospital, Malmö, Sweden.
Ify R MordiDivision of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.ORCID http://orcid.org/0000-0002-2686-729X
Michael P MorleyPenn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Andrew P MorrisDepartment of Biostatistics, University of Liverpool, Liverpool, UK.
Alanna C MorrisonDepartment of Epidemiology, Human Genetics, and Environmental Sciences, The University of Texas School of Public Health, Houston, TX, USA.ORCID http://orcid.org/0000-0001-6381-4296
Lori MortonCardiovascular Research, Regeneron Pharmaceuticals, Tarrytown, NY, USA.
Michael W NaglePfizer Worldwide Research & Development, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-4677-7582
Christopher P NelsonDepartment of Cardiovascular Sciences, University of Leicester and NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.ORCID http://orcid.org/0000-0001-8025-2897
Alexander NiessnerDepartment of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria.
Teemu NiiranenDepartment of Medicine, Turku University Hospital and University of Turku, Turku, Finland.ORCID http://orcid.org/0000-0002-7394-7487
Raymond NoordamSection of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.ORCID http://orcid.org/0000-0001-7801-809X
Christoph NowakDepartment of Neurobiology, Care Sciences and Society/Section of Family Medicine and Primary Care, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0001-8435-3978
Michelle L O'DonoghueTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, USA.
Sisse Rye OstrowskiDepartment of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.ORCID http://orcid.org/0000-0001-5288-3851
Anjali T OwensPenn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Colin N A PalmerDivision of Population Health and Genomics, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.ORCID http://orcid.org/0000-0002-6415-6560
Guillaume ParéDepartment of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.ORCID http://orcid.org/0000-0002-6795-4760
Ole Birger PedersenDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0003-2312-5976
Markus PerolaNational Institute for Health and Welfare, Helsinki, Finland.
Marie PigeyrePopulation Health Research Institute, Hamilton, Ontario, Canada.ORCID http://orcid.org/0000-0003-2984-8366
Bruce M PsatyCardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-7278-2190
Kenneth M RiceDepartment of Biostatistics, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-3071-7278
Paul M RidkerDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Simon P R RomaineDepartment of Cardiovascular Sciences, University of Leicester and NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
Jerome I RotterThe Institute for Translational Genomics and Population Sciences, Harbor-UCLA Medical Center, Torrance, CA, USA.
Christian T RuffTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, USA.
Marc S SabatineTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, USA.
Neneh SallahInstitute of Health Informatics, University College London, London, UK.ORCID http://orcid.org/0000-0002-2953-5311
Veikko SalomaaNational Institute for Health and Welfare, Helsinki, Finland.ORCID http://orcid.org/0000-0001-7563-5324
Naveed SattarBHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.ORCID http://orcid.org/0000-0002-1604-2593
Alaa A ShalabyDepartment of Medicine, Division of Cardiology, University of Pittsburgh Medical Center and VA Pittsburgh HCS, Pittsburgh, PA, USA.
Akshay ShekharCardiovascular Research, Regeneron Pharmaceuticals, Tarrytown, NY, USA.
Diane T SmelserDepartment of Molecular and Functional Genomics, Geisinger, Danville, PA, USA.
Nicholas L SmithKaiser Permanente Washington Health Research Institute, Kaiser Permanente Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0003-3483-353X
Erik SørensenDepartment of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-5002-9077
Sundararajan SrinivasanDivision of Population Health and Genomics, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.ORCID http://orcid.org/0000-0002-3387-9889
Kari StefanssondeCODE genetics/Amgen Inc., Reykjavik, Iceland.
Garðar SveinbjörnssondeCODE genetics/Amgen Inc., Reykjavik, Iceland.ORCID http://orcid.org/0000-0003-2429-9468
Per SvenssonDepartment of Cardiology, Söderjukhuset, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-0372-6272
Mari-Liis TammesooEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
Jean-Claude TardifMontreal Heart Institute, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0002-8200-8983
Maris Teder-LavingEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.ORCID http://orcid.org/0000-0002-5872-1850
Alexander TeumerDZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0002-8309-094X
Guðmundur ThorgeirssondeCODE genetics/Amgen Inc., Reykjavik, Iceland.ORCID http://orcid.org/0000-0002-7146-1395
Unnur ThorsteinsdottirdeCODE genetics/Amgen Inc., Reykjavik, Iceland.
Christian Torp-PedersenDepartment of Epidemiology and Biostatistics, Aalborg University Hospital, Aalborg, Denmark.ORCID http://orcid.org/0000-0003-2892-6131
Vinicius TragantedeCODE genetics/Amgen Inc., Reykjavik, Iceland.ORCID http://orcid.org/0000-0002-8223-8957
Stella TrompetDepartment of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.ORCID http://orcid.org/0000-0001-5006-0528
Andre G UitterlindenDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.ORCID http://orcid.org/0000-0002-7276-3387
Henrik UllumStatens Serum Institut, Copenhagen, Denmark.
Pim van der HarstDepartment of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
David van HeelCentre for Genomics and Child Health, Blizard Institute, Queen Mary University of London, London, UK.ORCID http://orcid.org/0000-0002-0637-2265
Jessica van SettenDepartment of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, the Netherlands.ORCID http://orcid.org/0000-0002-4934-7510
Marion van VugtDepartment of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, the Netherlands.ORCID http://orcid.org/0000-0002-6634-1989
Abirami VeluchamyDivision of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
Monique VerschuurenDepartment Life Course and Health, Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.ORCID http://orcid.org/0000-0003-2134-4227
Niek VerweijDepartment of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Christoffer Rasmus VissingDepartment of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-0834-206X
Uwe VölkerDZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0002-5689-3448
Adriaan A VoorsDepartment of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Lars WallentinUppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
Yunzhang WangDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-1165-3595
Peter E WeekeDepartment of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Kerri L WigginsDepartment of Medicine, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0003-2749-1279
L Keoki WilliamsCenter for Individualized and Genomic Medicine Research, Department of Internal Medicine, Henry Ford Hospital, Detroit, MI, USA.
Yifan YangPenn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Bing YuDepartment of Epidemiology, Human Genetics, and Environmental Sciences, The University of Texas School of Public Health, Houston, TX, USA.ORCID http://orcid.org/0000-0003-4818-1077
Faiez ZannadUniversité de Lorraine, CHU de Nancy, Inserm and INI-CRCT (F-CRIN), Institut Lorrain du Coeur et des Vaisseaux, Vandoeuvre Lès Nancy, France.ORCID http://orcid.org/0000-0001-7456-1570
Chaoqun ZhengDepartment of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-3248-8560
Genes & Health Research Team
Estonian Biobank Research Team
DBDS Genomic Consortium
Folkert W AsselbergsInstitute of Health Informatics, University College London, London, UK.
Thomas P CappolaPenn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-9630-7204
Marie-Pierre DubéMontreal Heart Institute, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0001-8442-4393
Michael E DunnCardiovascular Research, Regeneron Pharmaceuticals, Tarrytown, NY, USA.
Chim C LangDivision of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
Nilesh J SamaniDepartment of Cardiovascular Sciences, University of Leicester and NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
Svati ShahDepartment of Medicine, Division of Cardiology, Duke University Medical Center, Durham, NC, USA.
Ramachandran S Vasan *National Heart, Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, USA.ORCID http://orcid.org/0000-0001-7357-5970
J Gustav Smith *Department of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg University and Sahlgrenska University Hospital, Gothenburg, Sweden.
Hilma Holm *deCODE genetics/Amgen Inc., Reykjavik, Iceland.ORCID http://orcid.org/0000-0002-9517-6636
Sonia Shah *Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0001-5860-4526
Patrick T Ellinor *Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-2067-0533
Aroon D Hingorani *Institute of Cardiovascular Science, University College London, London, UK.ORCID http://orcid.org/0000-0001-8365-0081
Quinn Wells *Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN, USA.
R Thomas Lumbers *Institute of Health Informatics, University College London, London, UK. t.lumbers@ucl.ac.uk.ORCID http://orcid.org/0000-0002-9077-4741
HERMES Consortium

Funding

Genetic Architecture of Cardiac Structure and Function and Its Impact on Heart FailureR01HL160793 · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2025 to 2025
$702k
British Heart Foundation (BHF) AA/18/6/34223British Heart Foundation (BHF) FS/18/65/34186DH | National Institute for Health Research (NIHR) NIHR203328NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL160793NIA NIH HHS U01 AG068221
6 · The paper itself

Abstract

Heart failure (HF) is a major contributor to global morbidity and mortality. While distinct clinical subtypes, defined by etiology and left ventricular ejection fraction, are well recognized, their genetic determinants remain inadequately understood. In this study, we report a genome-wide association study of HF and its subtypes in a sample of 1.9 million individuals. A total of 153,174 individuals had HF, of whom 44,012 had a nonischemic etiology (ni-HF). A subset of patients with ni-HF were stratified based on left ventricular systolic function, where data were available, identifying 5,406 individuals with reduced ejection fraction and 3,841 with preserved ejection fraction. We identify 66 genetic loci associated with HF and its subtypes, 37 of which have not previously been reported. Using functionally informed gene prioritization methods, we predict effector genes for each identified locus, and map these to etiologic disease clusters through phenome-wide association analysis, network analysis and colocalization. Through heritability enrichment analysis, we highlight the role of extracardiac tissues in disease etiology. We then examine the differential associations of upstream risk factors with HF subtypes using Mendelian randomization. These findings extend our understanding of the mechanisms underlying HF etiology and may inform future approaches to prevention and treatment.

Indexed as

Genome-Wide Association StudyHeart FailureFemaleGenetic Predisposition to DiseaseHumansMalePolymorphism, Single NucleotideStroke VolumeVentricular Function, Left

Identifiers

PMID40038546
PMCPMC11985341

What Socratic holds

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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.