TY - JOUR
T1 - Genome-wide analyses of neonatal jaundice reveal a marked departure from adult bilirubin metabolism
AU - Solé-Navais, Pol
AU - Juodakis, Julius
AU - Ytterberg, Karin
AU - Wu, Xiaoping
AU - Bradfield, Jonathan P.
AU - Vaudel, Marc
AU - LaBella, Abigail L.
AU - Helgeland, Øyvind
AU - Flatley, Christopher
AU - Geller, Frank
AU - Finel, Moshe
AU - Zhao, Mengqi
AU - Lazarus, Philip
AU - Hakonarson, Hakon
AU - Magnus, Per
AU - Andreassen, Ole A.
AU - Njølstad, Pål R.
AU - Grant, Struan F.A.
AU - Feenstra, Bjarke
AU - Muglia, Louis J.
AU - Johansson, Stefan
AU - Zhang, Ge
AU - Jacobsson, Bo
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85202735020
U2 - 10.1038/s41467-024-51947-w
DO - 10.1038/s41467-024-51947-w
M3 - Article
C2 - 39214992
AN - SCOPUS:85202735020
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 7550
ER -