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Genome-wide analyses of neonatal jaundice reveal a marked departure from adult bilirubin metabolism

Author

Listed:
  • Pol Solé-Navais

    (University of Gothenburg)

  • Julius Juodakis

    (University of Gothenburg)

  • Karin Ytterberg

    (University of Gothenburg)

  • Xiaoping Wu

    (Statens Serum Institut
    Rigshospitalet)

  • Jonathan P. Bradfield

    (Children’s Hospital of Philadelphia
    Quantinuum Research LLC)

  • Marc Vaudel

    (University of Bergen
    Norwegian Institute of Public Health)

  • Abigail L. LaBella

    (University of North Carolina at Charlotte)

  • Øyvind Helgeland

    (University of Bergen
    Norwegian Institute of Public Health)

  • Christopher Flatley

    (University of Gothenburg)

  • Frank Geller

    (Statens Serum Institut
    Rigshospitalet)

  • Moshe Finel

    (University of Helsinki)

  • Mengqi Zhao

    (Washington State University)

  • Philip Lazarus

    (Washington State University
    University at Buffalo)

  • Hakon Hakonarson

    (Children’s Hospital of Philadelphia
    Children’s Hospital of Philadelphia
    University of Pennsylvania
    Children’s Hospital of Philadelphia)

  • Per Magnus

    (Norwegian Institute of Public Health)

  • Ole A. Andreassen

    (University of Oslo
    University of Oslo
    Oslo University Hospital)

  • Pål R. Njølstad

    (University of Bergen
    Haukeland University Hospital)

  • Struan F. A. Grant

    (Children’s Hospital of Philadelphia
    Children’s Hospital of Philadelphia
    University of Pennsylvania
    University of Pennsylvania)

  • Bjarke Feenstra

    (Statens Serum Institut
    Rigshospitalet
    University of Copenhagen)

  • Louis J. Muglia

    (Burroughs Wellcome Fund
    Cincinnati Children’s Hospital Medical Center
    University of Cincinnati College of Medicine)

  • Stefan Johansson

    (University of Bergen
    Haukeland University Hospital)

  • Ge Zhang

    (Cincinnati Children’s Hospital Medical Center
    University of Cincinnati College of Medicine)

  • Bo Jacobsson

    (University of Gothenburg
    Norwegian Institute of Public Health)

Abstract

Jaundice affects almost all neonates in their first days of life and is caused by the accumulation of bilirubin. Although the core biochemistry of bilirubin metabolism is well understood, it is not clear why some neonates experience more severe jaundice and require treatment with phototherapy. Here, we present the first genome-wide association study of neonatal jaundice to date in nearly 30,000 parent-offspring trios from Norway (cases ≈ 2000). The alternate allele of a common missense variant affecting the sequence of UGT1A4 reduces the susceptibility to jaundice five-fold, which replicated in separate cohorts of neonates of African American and European ancestries. eQTL colocalization analyses indicate that the association may be driven by regulation of UGT1A1 in the intestines, but not in the liver. Our results reveal marked differences in the genetic variants involved in neonatal jaundice compared to those regulating bilirubin levels in adults, suggesting distinct genetic mechanisms for the same biological pathways.

Suggested Citation

  • Pol Solé-Navais & Julius Juodakis & Karin Ytterberg & Xiaoping Wu & Jonathan P. Bradfield & Marc Vaudel & Abigail L. LaBella & Øyvind Helgeland & Christopher Flatley & Frank Geller & Moshe Finel & Men, 2024. "Genome-wide analyses of neonatal jaundice reveal a marked departure from adult bilirubin metabolism," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51947-w
    DOI: 10.1038/s41467-024-51947-w
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    References listed on IDEAS

    as
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    2. Xueping Liu & Dorte Helenius & Line Skotte & Robin N. Beaumont & Matthias Wielscher & Frank Geller & Julius Juodakis & Anubha Mahajan & Jonathan P. Bradfield & Frederick T. J. Lin & Suzanne Vogelezang, 2019. "Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
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