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Analysis of cardiac magnetic resonance imaging in 36,000 individuals yields genetic insights into dilated cardiomyopathy

Author

Listed:
  • James P. Pirruccello

    (Division of Cardiology, Massachusetts General Hospital
    Center for Genomic Medicine, Massachusetts General Hospital
    Program in Medical and Population Genetics, Broad Institute)

  • Alexander Bick

    (Center for Genomic Medicine, Massachusetts General Hospital
    Program in Medical and Population Genetics, Broad Institute
    Department of Medicine, Massachusetts General Hospital)

  • Minxian Wang

    (Program in Medical and Population Genetics, Broad Institute)

  • Mark Chaffin

    (Program in Medical and Population Genetics, Broad Institute)

  • Samuel Friedman

    (Data Sciences Platform, Broad Institute)

  • Jie Yao

    (The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center)

  • Xiuqing Guo

    (The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center)

  • Bharath Ambale Venkatesh

    (Department of Radiology, Johns Hopkins University)

  • Kent D. Taylor

    (The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center)

  • Wendy S. Post

    (Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health
    Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine)

  • Stephen Rich

    (Center for Public Health Genomics, University of Virginia)

  • Joao A. C. Lima

    (Department of Radiology, Johns Hopkins University
    Division of Cardiology, Johns Hopkins University School of Medicine)

  • Jerome I. Rotter

    (The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center)

  • Anthony Philippakis

    (Data Sciences Platform, Broad Institute)

  • Steven A. Lubitz

    (Division of Cardiology, Massachusetts General Hospital
    Center for Genomic Medicine, Massachusetts General Hospital
    Program in Medical and Population Genetics, Broad Institute
    Harvard Medical School)

  • Patrick T. Ellinor

    (Division of Cardiology, Massachusetts General Hospital
    Center for Genomic Medicine, Massachusetts General Hospital
    Program in Medical and Population Genetics, Broad Institute
    Harvard Medical School)

  • Amit V. Khera

    (Division of Cardiology, Massachusetts General Hospital
    Center for Genomic Medicine, Massachusetts General Hospital
    Program in Medical and Population Genetics, Broad Institute
    Harvard Medical School)

  • Sekar Kathiresan

    (Division of Cardiology, Massachusetts General Hospital
    Center for Genomic Medicine, Massachusetts General Hospital
    Program in Medical and Population Genetics, Broad Institute
    Harvard Medical School)

  • Krishna G. Aragam

    (Division of Cardiology, Massachusetts General Hospital
    Center for Genomic Medicine, Massachusetts General Hospital
    Program in Medical and Population Genetics, Broad Institute
    Harvard Medical School)

Abstract

Dilated cardiomyopathy (DCM) is an important cause of heart failure and the leading indication for heart transplantation. Many rare genetic variants have been associated with DCM, but common variant studies of the disease have yielded few associated loci. As structural changes in the heart are a defining feature of DCM, we report a genome-wide association study of cardiac magnetic resonance imaging (MRI)-derived left ventricular measurements in 36,041 UK Biobank participants, with replication in 2184 participants from the Multi-Ethnic Study of Atherosclerosis. We identify 45 previously unreported loci associated with cardiac structure and function, many near well-established genes for Mendelian cardiomyopathies. A polygenic score of MRI-derived left ventricular end systolic volume strongly associates with incident DCM in the general population. Even among carriers of TTN truncating mutations, this polygenic score influences the size and function of the human heart. These results further implicate common genetic polymorphisms in the pathogenesis of DCM.

Suggested Citation

  • James P. Pirruccello & Alexander Bick & Minxian Wang & Mark Chaffin & Samuel Friedman & Jie Yao & Xiuqing Guo & Bharath Ambale Venkatesh & Kent D. Taylor & Wendy S. Post & Stephen Rich & Joao A. C. Li, 2020. "Analysis of cardiac magnetic resonance imaging in 36,000 individuals yields genetic insights into dilated cardiomyopathy," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15823-7
    DOI: 10.1038/s41467-020-15823-7
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    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.
    2. Caibo Ning & Linyun Fan & Meng Jin & Wenji Wang & Zhiqiang Hu & Yimin Cai & Liangkai Chen & Zequn Lu & Ming Zhang & Can Chen & Yanmin Li & Fuwei Zhang & Wenzhuo Wang & Yizhuo Liu & Shuoni Chen & Yuan , 2023. "Genome-wide association analysis of left ventricular imaging-derived phenotypes identifies 72 risk loci and yields genetic insights into hypertrophic cardiomyopathy," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Jennifer L. Halford & Valerie N. Morrill & Seung Hoan Choi & Sean J. Jurgens & Giorgio Melloni & Nicholas A. Marston & Lu-Chen Weng & Victor Nauffal & Amelia W. Hall & Sophia Gunn & Christina A. Austi, 2022. "Endophenotype effect sizes support variant pathogenicity in monogenic disease susceptibility genes," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    4. 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.
    5. 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.
    6. 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.
    7. Adityanarayanan Radhakrishnan & Sam F. Friedman & Shaan Khurshid & Kenney Ng & Puneet Batra & Steven A. Lubitz & Anthony A. Philippakis & Caroline Uhler, 2023. "Cross-modal autoencoder framework learns holistic representations of cardiovascular state," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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