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Uncovering the heritable components of multimorbidities and disease trajectories using a nationwide cohort

Author

Listed:
  • David Westergaard

    (Faculty of Health and Medical Sciences, University of Copenhagen
    Statistics Denmark
    Copenhagen University Hospital Hvidovre)

  • Frederik Hytting Jørgensen

    (Statistics Denmark)

  • Jens Waaben

    (Faculty of Health and Medical Sciences, University of Copenhagen)

  • Alexander Wolfgang Jung

    (Faculty of Health and Medical Sciences, University of Copenhagen
    Statistics Denmark)

  • Mette Lademann

    (Faculty of Health and Medical Sciences, University of Copenhagen
    Statistics Denmark)

  • Thomas Folkmann Hansen

    (Faculty of Health and Medical Sciences, University of Copenhagen)

  • Jolien Cremers

    (Statistics Denmark
    University of Copenhagen)

  • Sisse Rye Ostrowski

    (Rigshospitalet, University of Copenhagen
    Faculty of Health and Medical Sciences, University of Copenhagen)

  • Ole Birger Vesterager Pedersen

    (Faculty of Health and Medical Sciences, University of Copenhagen
    Zealand University Hospital)

  • Roc Reguant

    (Faculty of Health and Medical Sciences, University of Copenhagen
    Commonwealth Scientific and Industrial Research Organisation, New South Wales)

  • Isabella Friis Jørgensen

    (Faculty of Health and Medical Sciences, University of Copenhagen)

  • Tom Fitzgerald

    (European Bioinformatics Institute)

  • Ewan Birney

    (European Bioinformatics Institute)

  • Karina Banasik

    (Faculty of Health and Medical Sciences, University of Copenhagen)

  • Laust Mortensen

    (Statistics Denmark
    University of Copenhagen)

  • Søren Brunak

    (Faculty of Health and Medical Sciences, University of Copenhagen)

Abstract

Quantifying the contribution of genetics and environmental effects on disease initiation and progression, as well as the shared genetics of different diseases, is vital for the understanding of the disease etiology of multimorbidities. In this study, we leverage nationwide Danish registries to provide a granular atlas of the genetic origin of disease phenotypes for a cohort of all Danes 1978–2018 with partially known pedigree (n = 6.3 million). We estimate the heritability and genetic correlation between thousands of disease phenotypes using a novel approach that can be scaled to nationwide data. Our findings confirm the importance of genetics for a number of known associations and increase the resolution of heritability by adding numerous associations, some of which point to shared biologically origin of different phenotypes. We also establish the heritability of disease trajectories and the importance of sex-specific genetic contributions. Results can be accessed at https://h2.cpr.ku.dk/ .

Suggested Citation

  • David Westergaard & Frederik Hytting Jørgensen & Jens Waaben & Alexander Wolfgang Jung & Mette Lademann & Thomas Folkmann Hansen & Jolien Cremers & Sisse Rye Ostrowski & Ole Birger Vesterager Pedersen, 2024. "Uncovering the heritable components of multimorbidities and disease trajectories using a nationwide cohort," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51795-8
    DOI: 10.1038/s41467-024-51795-8
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    References listed on IDEAS

    as
    1. Anders Boeck Jensen & Pope L. Moseley & Tudor I. Oprea & Sabrina Gade Ellesøe & Robert Eriksson & Henriette Schmock & Peter Bjødstrup Jensen & Lars Juhl Jensen & Søren Brunak, 2014. "Temporal disease trajectories condensed from population-wide registry data covering 6.2 million patients," Nature Communications, Nature, vol. 5(1), pages 1-10, September.
    2. David Westergaard & Pope Moseley & Freja Karuna Hemmingsen Sørup & Pierre Baldi & Søren Brunak, 2019. "Population-wide analysis of differences in disease progression patterns in men and women," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    3. Andrew D. Grotzinger & Mijke Rhemtulla & Ronald Vlaming & Stuart J. Ritchie & Travis T. Mallard & W. David Hill & Hill F. Ip & Riccardo E. Marioni & Andrew M. McIntosh & Ian J. Deary & Philipp D. Koel, 2019. "Genomic structural equation modelling provides insights into the multivariate genetic architecture of complex traits," Nature Human Behaviour, Nature, vol. 3(5), pages 513-525, May.
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