Nature communications · 2022
GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements.
СтатьяМетаанализПоддержка исследования: вне правительства СШАПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Dixon Peter H, Levine Adam P, Cebola Inês, Chan Melanie M Y, Amin Aliya S, Aich Anshul, Mozere Monika, Maude Hannah, Mitchell Alice L, Zhang Jun, NIHR BioResource, Genomics England Research Consortium Collaborators, Chambers Jenny, Syngelaki Argyro, Donnelly Jennifer, Cooley Sharon, Geary Michael, Nicolaides Kypros, Thorsell Malin, Hague William M, Estiu Maria Cecilia, Marschall Hanns-Ulrich, Gale Daniel P, Williamson Catherine
Аннотация
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.