Genome-wide analyses of neonatal jaundice reveal a marked departure from adult bilirubin metabolism.
Nat Commun
; 15(1): 7550, 2024 Aug 30.
Article
em En
| MEDLINE
| ID: mdl-39214992
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bilirrubina
/
Glucuronosiltransferase
/
Estudo de Associação Genômica Ampla
/
Icterícia Neonatal
Limite:
Adult
/
Female
/
Humans
/
Male
/
Newborn
País/Região como assunto:
Europa
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Suécia
País de publicação:
Reino Unido