GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

NIHR BioResource, Genomics England Research Consortium Collaborators, Peter H. Dixon, Adam Levine, Inês Cebola, Melanie M.Y. Chan, Aliya S. Amin, Anshul Aich, Monika Mozere, Hannah Maude, Alice L. Mitchell, Jun Zhang, Jennifer Chambers, Argyro Syngelaki, Jennifer Donnelly, Sharon Cooley, Michael Geary, Kypros H. Nicolaides, Malin Thorsell, William M. HagueMaria C. Estiu, Hanns Ulrich Marschall, Daniel P. Gale, Catherine Williamson

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility.
Original languageEnglish
Article number4840
JournalNature Communications
Volume13
Issue number1
DOIs
Publication statusPublished - Dec 2022

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