SynthesisNature communications2022
Genome-wide association and multi-trait analyses characterize the common genetic architecture of heart failure.
Open access · goldAbstract readMeta-Analysis
In one paragraph
Synthesis in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 10 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 10 pooled it
23.9field-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
88 citing papers in PubMed, 10 syntheses or guidelines pooled it, 139 citations in OpenAlex.
- Multi-ancestry genetic architecture of heart failure subtypes.Nature communications · 2026Pooled it
- Genome and Transcriptome-Wide Analyses Identify Multiple Candidate Genes and a Significant Polygenic Contribution in Bicuspid Aortic Valve.Circulation · 2026Pooled it
- Genome-wide analysis of heart failure yields insights into disease heterogeneity and enables prognostic prediction in the Japanese population.Nature communications · 2025Pooled it
- A systematic review of GWAS on CMR imaging traits: genetic insights into cardiovascular structure, function, and diseases.EBioMedicine · 2025Pooled it
- Genome-wide analysis identifies susceptibility loci for heart failure and nonischemic cardiomyopathy subtype in the East Asian populations.PLoS genetics · 2025Pooled it
- Cardiovascular diseases and depression: A meta-analysis and Mendelian randomization analysis.Molecular psychiatry · 2025Pooled it
- Pooled it
- Genome-wide association study meta-analysis provides insights into the etiology of heart failure and its subtypes.Nature genetics · 2025Pooled it
- Causal effects between atrial fibrillation and heart failure: evidence from a bidirectional Mendelian randomization study.BMC medical genomics · 2023Pooled it
- Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure.Nature communications · 2023Pooled it
- Translating genome-wide association studies at multiple scales: Drug target prioritization, cellular architectures, and organ imaging.Cell genomics · 2026Review
- Brain-heart-eye axis revealed by multi-organ imaging genetics and proteomics.Nature biomedical engineering · 2026Article
- Molecular Mechanisms and Multi-Omics Integration in Heart Failure: From Pathophysiology to Precision Medicine.International journal of molecular sciences · 2026Review
- Lp(a) Has Specific Effects on Coronary Artery Disease Independent of LDL-C: A Mendelian Randomization Study.JACC. Advances · 2026Article
- Angiographic Burden of Coronary Atherosclerosis Partially Mediates the Association Between ASCVD Risk Factors and Outcomes.Circulation. Genomic and precision medicine · 2026Article
- Surgical Repair of Multiple Coronary Artery Aneurysms With Multivessel Coronary Disease.JACC. Case reports · 2026Article
- BCAA Metabolic Dyshomeostasis in Cardiovascular Disease: Pathogenic Mechanisms and Intervention.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2026Review
- Genome-wide analysis of cardiac ventricular phenotypes reveals novel loci and therapeutic targets for heart failure.Nature communications · 2026Article
- Multi-organ AI endophenotypes chart the heterogeneity of brain, eye and heart pan-disease.Nature. Mental health · 2026Article
- Associations of physical frailty and polygenic score with incident heart failure in cardiovascular patients: unraveling the mediating role of inflammation.GeroScience · 2026Article
28 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
44 authors at 17 institutions in 1 country.
Michael G LevinDivision of Cardiovascular Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-9937-9932
Noah L TsaoDepartment of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID 0000-0002-5743-0795
Pankhuri SinghalDepartment of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Chang LiuDepartment of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.ORCID 0000-0002-8918-7224
Ha My T VyThe Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Ishan ParanjpeDepartment of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Joshua D BackmanRegeneron Genetics Center, Tarrytown, NY, USA.ORCID 0000-0001-7262-0880
Tiffany R BellomoDepartment of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
William P BoneGenomics and Computational Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Kiran J BiddingerCenter for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Qin HuiEmory University School of Public Health, Atlanta, GA, USA.ORCID 0000-0002-8421-3518
Ozan DikilitasDepartments of Internal Medicine and Cardiovascular Medicine, and Mayo Clinician-Investigator Training Program, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-9906-8608
Benjamin A SatterfieldDepartment of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-7798-0938
Yifan YangCardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Michael P MorleyCardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Yuki BradfordDepartment of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Megan BurkeDivision of Cardiovascular Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0001-6735-8208
Nosheen RezaDivision of Cardiovascular Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Brian CharestMassachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston, MA, USA.
Regeneron Genetics Center
Renae L JudyDepartment of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Megan J PuckelwartzDepartment of Pharmacology, Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID 0000-0002-0455-2983
Hakon HakonarsonCenter for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Atlas KhanDivision of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA.ORCID 0000-0002-6651-2725
Leah C KottyanDepartment of Pediatrics, Division of Human Genetics and Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.ORCID 0000-0003-3979-2220
Iftikhar KulloDepartment of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-6524-3471
Yuan LuoDepartment of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.ORCID 0000-0003-0195-7456
Elizabeth M McNallyCenter for Genetic Medicine, Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Laura J Rasmussen-TorvikDepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Sharlene M DayDivision of Cardiovascular Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Ron DoThe Charles Bronfman Institute for Personalized Medicine, BioMe Phenomics Center, and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-3144-3627
Lawrence S PhillipsAtlanta VA Health Care System, Decatur, GA, USA.
Patrick T EllinorProgram in Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-2067-0533
Girish N NadkarniDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0001-6319-4314
Marylyn D RitchieDepartment of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID 0000-0002-1208-1720
Zoltan AranyDivision of Cardiovascular Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0003-1368-2453
Thomas P CappolaDivision of Cardiovascular Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Kenneth B MarguliesDivision of Cardiovascular Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Krishna G AragamCenter for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-3223-9131
Christopher M HaggertyDepartment of Translational Data Science and Informatics and Heart Institute, Geisinger, Danville, PA, USA.ORCID 0000-0002-3227-4490
Jacob JosephMassachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston, MA, USA.
Yan V SunEmory University School of Public Health, Atlanta, GA, USA.ORCID 0000-0002-2838-1824
Benjamin F VoightDepartment of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID 0000-0002-6205-9994
Scott M DamrauerCorporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA. damrauer@upenn.edu.ORCID 0000-0001-8009-1632
University of Pennsylvania · USCardiovascular Institute of the South · USEmory University · USNorthwestern University · USBroad Institute · USIcahn School of Medicine at Mount Sinai · USMayo Clinic in Arizona · USPhiladelphia VA Medical Center · USBrigham and Women's Hospital · USChildren's Hospital of Philadelphia · USCincinnati Children's Hospital Medical Center · USColumbia University · USGeisinger Neuroscience Institute · USRegeneron (United States) · USStanford University · USTranslational Therapeutics (United States) · USVA Boston Healthcare System · US
Funding
Northwestern University Clinical and Translational Science Institute (NUCATS)UL1TR001422 · NCATS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI D'AQUILA, RICHARD · 2015 to 2023
$56.8MInstitutional Clinical and Translational Science AwardKL2TR001879 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI MEAGHER, EMMA ANNE · 2016 to 2025
$13.7MTraining Program in Cardiovascular Biology and MedicineT32HL007843 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI THOMAS P. CAPPOLA, Sharlene M Day · 1996 to 2026
$11.0MResearch Design, Data, and Analytics CoreP30DK092949 · NIDDK · UNIVERSITY OF CHICAGO · PI ELBERT S. HUANG · 2011 to 2026
$10.0MNRSA Training CoreTL1TR001880 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI MEAGHER, EMMA ANNE · 2016 to 2025
$10.0MIntegrative genomics of human heart failureR01HL105993 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI ASHLEY, EUAN A, CAPPOLA, THOMAS P. · 2011 to 2014
$8.9MFunctional Interrogation of T2D-associated genes in human stem cell-derived models and miceUM1DK126194 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI GRANT, STRUAN F A, KAESTNER, KLAUS H · 2020 to 2024
$8.8MNorthwestern Genomic Risk Assessment and Management ProgramU01HG011169 · NHGRI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI REX L CHISHOLM, Elizabeth M McNally · 2020 to 2026
$7.4MPolygenic Risk Scores for Healthier African American FamiliesU01HG011172 · NHGRI · CINCINNATI CHILDRENS HOSP MED CTR · PI Leah Claire Kottyan, LISA J MARTIN · 2020 to 2026
$7.2MCardiomyopathy Genomes ProjectR01HL128075 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI MCNALLY, ELIZABETH M, NOBREGA, MARCELO A. · 2015 to 2023
$5.3MMTSS1 in Myocardial DiseaseR01HL141232 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI THOMAS P. CAPPOLA, Scott Michael Damrauer · 2019 to 2026
$4.7MBranched chain amino acids in heart failureR01HL152446 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI Zoltan P Arany · 2020 to 2026
$3.7MBLRD VA I01 BX004821BLRD VA I01 BX005831CSRD VA I01 CX001737CSRD VA IK2 CX001780NCATS NIH HHS KL2 TR001879NCATS NIH HHS TL1 TR001880NCATS NIH HHS UL1 TR001422NHGRI NIH HHS U01 HG011169NHGRI NIH HHS U01 HG011172NHLBI NIH HHS R01 HL105993NHLBI NIH HHS R01 HL128075NHLBI NIH HHS R01 HL141232NHLBI NIH HHS R01 HL152446NHLBI NIH HHS T32 HL007843NHLBI NIH HHS U01 HL160279NIA NIH HHS F31 AG069441NIDDK NIH HHS P30 DK092949NIDDK NIH HHS R01 DK101478NIDDK NIH HHS R56 DK101478NIDDK NIH HHS UM1 DK126194NIH HHS S10 OD026880NIH HHS S10 OD030463
Abstract
Heart failure is a leading cause of cardiovascular morbidity and mortality. However, the contribution of common genetic variation to heart failure risk has not been fully elucidated, particularly in comparison to other common cardiometabolic traits. We report a multi-ancestry genome-wide association study meta-analysis of all-cause heart failure including up to 115,150 cases and 1,550,331 controls of diverse genetic ancestry, identifying 47 risk loci. We also perform multivariate genome-wide association studies that integrate heart failure with related cardiac magnetic resonance imaging endophenotypes, identifying 61 risk loci. Gene-prioritization analyses including colocalization and transcriptome-wide association studies identify known and previously unreported candidate cardiomyopathy genes and cellular processes, which we validate in gene-expression profiling of failing and healthy human hearts. Colocalization, gene expression profiling, and Mendelian randomization provide convergent evidence for the roles of BCKDHA and circulating branch-chain amino acids in heart failure and cardiac structure. Finally, proteome-wide Mendelian randomization identifies 9 circulating proteins associated with heart failure or quantitative imaging traits. These analyses highlight similarities and differences among heart failure and associated cardiovascular imaging endophenotypes, implicate common genetic variation in the pathogenesis of heart failure, and identify circulating proteins that may represent cardiomyopathy treatment targets.
Indexed as
Genome-Wide Association StudyHeart FailureGene Expression ProfilingGenetic Predisposition to DiseaseHeartHumansPhenotypePolymorphism, Single Nucleotide
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY
Read underepoch 390
Registered trials
None linked
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 OpenQuestion graph.