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

Autor: Dixon PH; Department of Women and Children's Health, School of Life Course Sciences, King's College London, London, UK., Levine AP; Department of Renal Medicine, University College London, London, UK.; Research Department of Pathology, University College London, London, UK., Cebola I; Section of Genetics and Genomics, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK., Chan MMY; Department of Renal Medicine, University College London, London, UK., Amin AS; Department of Women and Children's Health, School of Life Course Sciences, King's College London, London, UK., Aich A; Department of Renal Medicine, University College London, London, UK., Mozere M; Department of Renal Medicine, University College London, London, UK., Maude H; Section of Genetics and Genomics, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK., Mitchell AL; Department of Women and Children's Health, School of Life Course Sciences, King's College London, London, UK., Zhang J; Department of Renal Medicine, University College London, London, UK.; Division of Nephrology, Department of Medicine, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China., Chambers J; ICP Support, 69 Mere Green Road, Sutton Coldfield, UK.; Women's Health Research Centre, Imperial College London, London, UK., Syngelaki A; Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK., Donnelly J; The Rotunda Hospital, Dublin, Ireland., Cooley S; The Rotunda Hospital, Dublin, Ireland., Geary M; The Rotunda Hospital, Dublin, Ireland., Nicolaides K; Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK., Thorsell M; BB Stockholm, Danderyd Hospital, Stockholm, Sweden., Hague WM; Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia., Estiu MC; Ramón Sardá Mother's and Children's Hospital, Buenos Aires, Argentina., Marschall HU; Department of Molecular and Clinical Medicine/Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden., Gale DP; Department of Renal Medicine, University College London, London, UK., Williamson C; Department of Women and Children's Health, School of Life Course Sciences, King's College London, London, UK. catherine.williamson@kcl.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Aug 17; Vol. 13 (1), pp. 4840. Date of Electronic Publication: 2022 Aug 17.
DOI: 10.1038/s41467-022-29931-z
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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