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

David Westergaard, Frederik Hytting Jørgensen, Jens Waaben, Alexander Wolfgang Jung, Mette Lademann, Thomas Folkmann Hansen, Jolien Cremers, Sisse Rye Ostrowski, Ole Birger Vesterager Pedersen, Roc Reguant, Isabella Friis Jørgensen, Tom Fitzgerald, Ewan Birney, Karina Banasik, Laust Mortensen and Søren Brunak ()
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David Westergaard: Faculty of Health and Medical Sciences, University of Copenhagen
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
Mette Lademann: Faculty of Health and Medical Sciences, University of Copenhagen
Thomas Folkmann Hansen: Faculty of Health and Medical Sciences, University of Copenhagen
Jolien Cremers: Statistics Denmark
Sisse Rye Ostrowski: Rigshospitalet, University of Copenhagen
Ole Birger Vesterager Pedersen: Faculty of Health and Medical Sciences, University of Copenhagen
Roc Reguant: Faculty of Health and Medical Sciences, University of Copenhagen
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
Søren Brunak: Faculty of Health and Medical Sciences, University of Copenhagen

Nature Communications, 2024, vol. 15, issue 1, 1-11

Abstract: 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/ .

Date: 2024
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DOI: 10.1038/s41467-024-51795-8

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