IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-35323-0.html
   My bibliography  Save this article

Genetic architecture of heart failure with preserved versus reduced ejection fraction

Author

Listed:
  • Jacob Joseph

    (VA Boston Healthcare System
    Brigham and Women’s Hospital, Harvard Medical School
    VA Providence Healthcare System)

  • Chang Liu

    (Emory University Rollins School of Public Health)

  • Qin Hui

    (Emory University Rollins School of Public Health
    Atlanta VA Health Care System)

  • Krishna Aragam

    (VA Boston Healthcare System
    Massachusetts General Hospital
    Broad Institute of Harvard and MIT)

  • Zeyuan Wang

    (Emory University Rollins School of Public Health
    Atlanta VA Health Care System)

  • Brian Charest

    (VA Boston Healthcare System)

  • Jennifer E. Huffman

    (VA Boston Healthcare System)

  • Jacob M. Keaton

    (National Institutes of Health
    Vanderbilt University Medical Center)

  • Todd L. Edwards

    (Vanderbilt University Medical Center)

  • Serkalem Demissie

    (VA Boston Healthcare System
    Boston University School of Medicine)

  • Luc Djousse

    (VA Boston Healthcare System
    Brigham and Women’s Hospital, Harvard Medical School)

  • Juan P. Casas

    (VA Boston Healthcare System
    Brigham and Women’s Hospital, Harvard Medical School)

  • J. Michael Gaziano

    (VA Boston Healthcare System
    Brigham and Women’s Hospital, Harvard Medical School)

  • Kelly Cho

    (VA Boston Healthcare System
    Brigham and Women’s Hospital, Harvard Medical School)

  • Peter W. F. Wilson

    (Atlanta VA Health Care System
    Emory University School of Medicine)

  • Lawrence S. Phillips

    (Atlanta VA Health Care System
    Emory University School of Medicine)

  • Christopher J. O’Donnell

    (VA Boston Healthcare System
    Brigham and Women’s Hospital, Harvard Medical School)

  • Yan V. Sun

    (Emory University Rollins School of Public Health
    Atlanta VA Health Care System)

Abstract

Pharmacologic clinical trials for heart failure with preserved ejection fraction have been largely unsuccessful as compared to those for heart failure with reduced ejection fraction. Whether differences in the genetic underpinnings of these major heart failure subtypes may provide insights into the disparate outcomes of clinical trials remains unknown. We utilize a large, uniformly phenotyped, single cohort of heart failure sub-classified into heart failure with reduced and with preserved ejection fractions based on current clinical definitions, to conduct detailed genetic analyses of the two heart failure sub-types. We find different genetic architectures and distinct genetic association profiles between heart failure with reduced and with preserved ejection fraction suggesting differences in underlying pathobiology. The modest genetic discovery for heart failure with preserved ejection fraction (one locus) compared to heart failure with reduced ejection fraction (13 loci) despite comparable sample sizes indicates that clinically defined heart failure with preserved ejection fraction likely represents the amalgamation of several, distinct pathobiological entities. Development of consensus sub-phenotyping of heart failure with preserved ejection fraction is paramount to better dissect the underlying genetic signals and contributors to this highly prevalent condition.

Suggested Citation

  • Jacob Joseph & Chang Liu & Qin Hui & Krishna Aragam & Zeyuan Wang & Brian Charest & Jennifer E. Huffman & Jacob M. Keaton & Todd L. Edwards & Serkalem Demissie & Luc Djousse & Juan P. Casas & J. Micha, 2022. "Genetic architecture of heart failure with preserved versus reduced ejection fraction," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35323-0
    DOI: 10.1038/s41467-022-35323-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-35323-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-35323-0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Claudia Giambartolomei & Damjan Vukcevic & Eric E Schadt & Lude Franke & Aroon D Hingorani & Chris Wallace & Vincent Plagnol, 2014. "Bayesian Test for Colocalisation between Pairs of Genetic Association Studies Using Summary Statistics," PLOS Genetics, Public Library of Science, vol. 10(5), pages 1-15, May.
    2. Cristian Pattaro & Alexander Teumer & Mathias Gorski & Audrey Y. Chu & Man Li & Vladan Mijatovic & Maija Garnaas & Adrienne Tin & Rossella Sorice & Yong Li & Daniel Taliun & Matthias Olden & Meredith , 2016. "Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function," Nature Communications, Nature, vol. 7(1), pages 1-19, April.
    3. Tune H. Pers & Juha M. Karjalainen & Yingleong Chan & Harm-Jan Westra & Andrew R. Wood & Jian Yang & Julian C. Lui & Sailaja Vedantam & Stefan Gustafsson & Tonu Esko & Tim Frayling & Elizabeth K. Spel, 2015. "Biological interpretation of genome-wide association studies using predicted gene functions," Nature Communications, Nature, vol. 6(1), pages 1-9, May.
    4. Clare Bycroft & Colin Freeman & Desislava Petkova & Gavin Band & Lloyd T. Elliott & Kevin Sharp & Allan Motyer & Damjan Vukcevic & Olivier Delaneau & Jared O’Connell & Adrian Cortes & Samantha Welsh &, 2018. "The UK Biobank resource with deep phenotyping and genomic data," Nature, Nature, vol. 562(7726), pages 203-209, October.
    5. Adam E. Locke & Bratati Kahali & Sonja I. Berndt & Anne E. Justice & Tune H. Pers & Felix R. Day & Corey Powell & Sailaja Vedantam & Martin L. Buchkovich & Jian Yang & Damien C. Croteau-Chonka & Tonu , 2015. "Genetic studies of body mass index yield new insights for obesity biology," Nature, Nature, vol. 518(7538), pages 197-206, February.
    6. Sonia Shah & Albert Henry & Carolina Roselli & Honghuang Lin & Garðar Sveinbjörnsson & Ghazaleh Fatemifar & Åsa K. Hedman & Jemma B. Wilk & Michael P. Morley & Mark D. Chaffin & Anna Helgadottir & Nie, 2020. "Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    7. Marios Arvanitis & Emmanouil Tampakakis & Yanxiao Zhang & Wei Wang & Adam Auton & Diptavo Dutta & Stephanie Glavaris & Ali Keramati & Nilanjan Chatterjee & Neil C. Chi & Bing Ren & Wendy S. Post & Ale, 2020. "Genome-wide association and multi-omic analyses reveal ACTN2 as a gene linked to heart failure," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Danielle Rasooly & Gina M. Peloso & Alexandre C. Pereira & Hesam Dashti & Claudia Giambartolomei & Eleanor Wheeler & Nay Aung & Brian R. Ferolito & Maik Pietzner & Eric H. Farber-Eger & Quinn Stanton , 2023. "Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Lili Liu & Atlas Khan & Elena Sanchez-Rodriguez & Francesca Zanoni & Yifu Li & Nicholas Steers & Olivia Balderes & Junying Zhang & Priya Krithivasan & Robert A. LeDesma & Clara Fischman & Scott J. Heb, 2022. "Genetic regulation of serum IgA levels and susceptibility to common immune, infectious, kidney, and cardio-metabolic traits," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Amil M. Shah & Peder L. Myhre & Victoria Arthur & Pranav Dorbala & Humaira Rasheed & Leo F. Buckley & Brian Claggett & Guning Liu & Jianzhong Ma & Ngoc Quynh Nguyen & Kunihiro Matsushita & Chiadi Ndum, 2024. "Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Chamlee Cho & Beomsu Kim & Dan Say Kim & Mi Yeong Hwang & Injeong Shim & Minku Song & Yeong Chan Lee & Sang-Hyuk Jung & Sung Kweon Cho & Woong-Yang Park & Woojae Myung & Bong-Jo Kim & Ron Do & Hyon K., 2024. "Large-scale cross-ancestry genome-wide meta-analysis of serum urate," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    4. Katherine A. Kentistou & Jian’an Luan & Laura B. L. Wittemans & Catherine Hambly & Lucija Klaric & Zoltán Kutalik & John R. Speakman & Nicholas J. Wareham & Timothy J. Kendall & Claudia Langenberg & J, 2023. "Large scale phenotype imputation and in vivo functional validation implicate ADAMTS14 as an adiposity gene," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    5. Saaket Agrawal & Minxian Wang & Marcus D. R. Klarqvist & Kirk Smith & Joseph Shin & Hesam Dashti & Nathaniel Diamant & Seung Hoan Choi & Sean J. Jurgens & Patrick T. Ellinor & Anthony Philippakis & Me, 2022. "Inherited basis of visceral, abdominal subcutaneous and gluteofemoral fat depots," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    6. Rosalie B. T. M. Sterenborg & Inga Steinbrenner & Yong Li & Melissa N. Bujnis & Tatsuhiko Naito & Eirini Marouli & Tessel E. Galesloot & Oladapo Babajide & Laura Andreasen & Arne Astrup & Bjørn Olav Å, 2024. "Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    7. Natalie DeForest & Yuqi Wang & Zhiyi Zhu & Jacqueline S. Dron & Ryan Koesterer & Pradeep Natarajan & Jason Flannick & Tiffany Amariuta & Gina M. Peloso & Amit R. Majithia, 2024. "Genome-wide discovery and integrative genomic characterization of insulin resistance loci using serum triglycerides to HDL-cholesterol ratio as a proxy," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    8. Sylvia Hartmann & Summaira Yasmeen & Benjamin M. Jacobs & Spiros Denaxas & Munir Pirmohamed & Eric R. Gamazon & Mark J. Caulfield & Harry Hemingway & Maik Pietzner & Claudia Langenberg, 2023. "ADRA2A and IRX1 are putative risk genes for Raynaud’s phenomenon," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    9. Brittany L. Mitchell & Jake R. Saklatvala & Nick Dand & Fiona A. Hagenbeek & Xin Li & Josine L. Min & Laurent Thomas & Meike Bartels & Jouke Hottenga & Michelle K. Lupton & Dorret I. Boomsma & Xianjun, 2022. "Genome-wide association meta-analysis identifies 29 new acne susceptibility loci," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    10. Zhaotong Lin & Wei Pan, 2024. "A robust cis-Mendelian randomization method with application to drug target discovery," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    11. Shaan Khurshid & Julieta Lazarte & James P. Pirruccello & Lu-Chen Weng & Seung Hoan Choi & Amelia W. Hall & Xin Wang & Samuel F. Friedman & Victor Nauffal & Kiran J. Biddinger & Krishna G. Aragam & Pu, 2023. "Clinical and genetic associations of deep learning-derived cardiac magnetic resonance-based left ventricular mass," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    12. Michael G. Levin & Noah L. Tsao & Pankhuri Singhal & Chang Liu & Ha My T. Vy & Ishan Paranjpe & Joshua D. Backman & Tiffany R. Bellomo & William P. Bone & Kiran J. Biddinger & Qin Hui & Ozan Dikilitas, 2022. "Genome-wide association and multi-trait analyses characterize the common genetic architecture of heart failure," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    13. Dixon, Padraig & Hollingworth, William & Harrison, Sean & Davies, Neil M. & Davey Smith, George, 2020. "Mendelian Randomization analysis of the causal effect of adiposity on hospital costs," Journal of Health Economics, Elsevier, vol. 70(C).
    14. Jordi Manuello & Joosung Min & Paul McCarthy & Fidel Alfaro-Almagro & Soojin Lee & Stephen Smith & Lloyd T. Elliott & Anderson M. Winkler & Gwenaëlle Douaud, 2024. "The effects of genetic and modifiable risk factors on brain regions vulnerable to ageing and disease," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    15. Xingjie Hao & Zhonghe Shao & Ning Zhang & Minghui Jiang & Xi Cao & Si Li & Yunlong Guan & Chaolong Wang, 2023. "Integrative genome-wide analyses identify novel loci associated with kidney stones and provide insights into its genetic architecture," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    16. James P. Pirruccello & Paolo Achille & Seung Hoan Choi & Joel T. Rämö & Shaan Khurshid & Mahan Nekoui & Sean J. Jurgens & Victor Nauffal & Shinwan Kany & Kenney Ng & Samuel F. Friedman & Puneet Batra , 2024. "Deep learning of left atrial structure and function provides link to atrial fibrillation risk," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    17. Shiyu Zhang & Zheng Wang & Yijing Wang & Yixiao Zhu & Qiao Zhou & Xingxing Jian & Guihu Zhao & Jian Qiu & Kun Xia & Beisha Tang & Julian Mutz & Jinchen Li & Bin Li, 2024. "A metabolomic profile of biological aging in 250,341 individuals from the UK Biobank," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    18. Magdalena Zimoń & Yunfeng Huang & Anthi Trasta & Aliaksandr Halavatyi & Jimmy Z. Liu & Chia-Yen Chen & Peter Blattmann & Bernd Klaus & Christopher D. Whelan & David Sexton & Sally John & Wolfgang Hube, 2021. "Pairwise effects between lipid GWAS genes modulate lipid plasma levels and cellular uptake," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    19. Diana Dunca & Sandesh Chopade & María Gordillo-Marañón & Aroon D. Hingorani & Karoline Kuchenbaecker & Chris Finan & Amand F. Schmidt, 2024. "Comparing the effects of CETP in East Asian and European ancestries: a Mendelian randomization study," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    20. Wenhan Chen & Yang Wu & Zhili Zheng & Ting Qi & Peter M. Visscher & Zhihong Zhu & Jian Yang, 2021. "Improved analyses of GWAS summary statistics by reducing data heterogeneity and errors," Nature Communications, Nature, vol. 12(1), pages 1-10, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35323-0. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.