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

Simple item page
dc.contributor.authorDixon, P.H.
dc.contributor.authorLevine, A.P.
dc.contributor.authorCebola, I.
dc.contributor.authorChan, M.M.Y.
dc.contributor.authorAmin, A.S.
dc.contributor.authorAich, A.
dc.contributor.authorMozere, M.
dc.contributor.authorMaude, H.
dc.contributor.authorMitchell, A.L.
dc.contributor.authorZhang, J.
dc.contributor.authorNIHR BioResource,
dc.contributor.authorGenomics England Research Consortium Collaborators,
dc.contributor.authorChambers, J.
dc.contributor.authorSyngelaki, A.
dc.contributor.authorDonnelly, J.
dc.contributor.authorCooley, S.
dc.contributor.authorGeary, M.
dc.contributor.authorNicolaides, K.
dc.contributor.authorThorsell, M.
dc.contributor.authorHague, W.M.
dc.contributor.authoret al.
dc.date.issued2022
dc.description.abstractIntrahepatic 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.
dc.description.statementofresponsibilityPeter H. Dixon ... William M. Hague ... et al.
dc.identifier.citationNature Communications, 2022; 13(1):4840-1-4840-18
dc.identifier.doi10.1038/s41467-022-29931-z
dc.identifier.issn2041-1723
dc.identifier.issn2041-1723
dc.identifier.orcidHague, W.M. [0000-0002-5355-2955]
dc.identifier.urihttps://hdl.handle.net/2440/146090
dc.language.isoen
dc.publisherNature Portfolio
dc.rights© The Author(s) 2022, corrected publication 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.
dc.source.urihttps://doi.org/10.1038/s41467-022-29931-z
dc.subjectGene expression profiling; Genome-wide association studies; Liver diseases
dc.subject.meshHumans
dc.subject.meshCholestasis, Intrahepatic
dc.subject.meshPregnancy Complications
dc.subject.meshPremature Birth
dc.subject.meshBile Acids and Salts
dc.subject.meshPregnancy
dc.subject.meshInfant, Newborn
dc.subject.meshFemale
dc.subject.meshGenome-Wide Association Study
dc.titleGWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements.
dc.typeJournal article
pubs.publication-statusPublished

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
hdl_146090.pdf
Size:
1.79 MB
Format:
Adobe Portable Document Format
Description:
Published version
Download

Collections

Research Outputs