Genome-wide analyses of neonatal jaundice reveal a marked departure from adult bilirubin metabolism
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.
Authors
- Moshe Finel (ORCID: https://orcid.org/0000-0003-1775-854X)
- Øyvind Helgeland (ORCID: https://orcid.org/0000-0002-5612-2985)
- Per Magnus (ORCID: https://orcid.org/0000-0002-6427-4735)
- Pål R. Njølstad (ORCID: https://orcid.org/0000-0003-0304-6728)
- Pol Solé-Navais (ORCID: https://orcid.org/0000-0002-3326-266X)
- Bjarke Feenstra (ORCID: https://orcid.org/0000-0003-1478-649X)
- Ole A. Andreassen (ORCID: https://orcid.org/0000-0002-4461-3568)
- Stefan E. Johansson (ORCID: https://orcid.org/0000-0002-2298-7008)
- Karin Ytterberg (ORCID: https://orcid.org/0000-0002-4314-1546)
- Marc Vaudel (ORCID: https://orcid.org/0000-0003-1179-9578)
- Frank Geller (ORCID: https://orcid.org/0000-0002-9238-3269)
- Christopher Flatley (ORCID: https://orcid.org/0000-0002-2225-0188)
- Struan F.A. Grant (ORCID: https://orcid.org/0000-0003-2025-5302)
- Abigail L. LaBella (ORCID: https://orcid.org/0000-0003-0068-6703)
- Julius Juodakis (ORCID: https://orcid.org/0000-0001-5600-974X)
- Louis J. Muglia
- Philip Lazarus (ORCID: https://orcid.org/0000-0002-8686-0874)
- Håkon Håkonarson (ORCID: https://orcid.org/0000-0003-2814-7461)
- Bo Jacobsson (ORCID: https://orcid.org/0000-0001-5079-2374)
- Xiaoping Wu (ORCID: https://orcid.org/0000-0002-7844-1397)
- Mengqi Zhao (ORCID: https://orcid.org/0009-0003-7345-1945)
- Ge Zhang (ORCID: https://orcid.org/0000-0001-9380-1357)
- Jonathan P. Bradfield
Institutions
- Statens Serum Institut (DK)
- University of North Carolina at Charlotte (US)
- University of Copenhagen (DK)
- Oslo University Hospital (NO)
- Cincinnati Children's Hospital Medical Center (US)
- Norwegian Institute of Public Health (NO)
- Children's Hospital of Philadelphia (US)
- University of Helsinki (FI)
- Washington State University Spokane (US)
- University of Oslo (NO)
- Burroughs Wellcome Fund (US)
- Haukeland University Hospital (NO)
- Copenhagen University Hospital (DK)
- Rigshospitalet (DK)
- Praevium Research (United States) (US)
- University of Bergen (NO)
- University at Buffalo, State University of New York (US)
- University of Pennsylvania (US)
- University of Gothenburg (SE)
- University of Cincinnati Medical Center (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-08-30
- DOI
- https://doi.org/10.1038/s41467-024-51947-w
- Citations
- 9
- Primary Topic
- Neonatal Health and Biochemistry
- Type
- article
- Field-Weighted Citation Impact
- 9.98
Funders
- March of Dimes Foundation
- Stiftelsen Kristian Gerhard Jebsen
- Trond Mohn stiftelse
- Helse- og Omsorgsdepartementet
- Novo Nordisk
- Vetenskapsrådet
- Universitetet i Bergen
- Norges Forskningsråd
- Göteborgs Universitet
- Novo Nordisk Fonden
- National Institutes of Health
- March of Dimes Prematurity Research Center Ohio Collaborative
- Norwegian Institute of Public Health