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

Lookup NU author(s): Dr Tina Biss, Dr Paul Brennan, Philip Griffiths, Professor Rita HorvathORCiD, Professor Patrick Chinnery, Dr Patrick Yu Wai Man, Dr Sally Johnson



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2022, The Author(s). 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.

Publication metadata

Author(s): Dixon PH, Levine AP, Cebola I, Gale DP, Williamson C, et al, NIHR BioResource, Genomics England Research Consortium, Biss TT, Brennan P, Griffiths PG, Horvath R, Chinnery PF, Yu Wai Man P, Johnson SA

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2022

Volume: 13

Issue: 1

Online publication date: 17/08/2022

Acceptance date: 08/04/2022

Date deposited: 28/06/2023

ISSN (electronic): 2041-1723

Publisher: Springer Nature


DOI: 10.1038/s41467-022-29931-z

PubMed id: 35977952


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Funder referenceFunder name
British Heart Foundation
Diabetes UK
Global Challenges Research Fund
Government Department for Business, Energy and Industrial Strategy
Wellcome Trust