DNA methylation profile of liver tissue in end-stage cholestatic liver disease

Angela C. Cheung, Brian D. Juran, Erik M. Schlicht, Bryan M. McCauley, Elizabeth J. Atkinson, Raymond Moore, Julie K. Heimbach, Kymberly D. Watt, Tsung Teh Wu, Nicholas F. Larusso, Gregory J. Gores, Zhifu Sun, Konstantinos N. Lazaridis

Research output: Contribution to journalArticlepeer-review


Aims: In this methylome-wide association study of cholestatic liver diseases (primary sclerosing cholangitis and primary biliary cholangitis), the authors aimed to elucidate changes in methylome and pathway enrichment to identify candidate genes. Patients methods: Reduced representation bisulfite sequencing was performed on liver tissue from 58 patients with primary sclerosing cholangitis (n = 13), primary biliary cholangitis (n = 20), alcoholic liver disease (n = 21) and live liver donors (n = 4). Pathway enrichment and network analysis were used to explore key genes/pathways. Results: Both cholestatic liver diseases were characterized by global hypomethylation, with pathway enrichment demonstrating distinct genes and pathways associated with the methylome. Conclusions: This novel study demonstrated that differential methylation in cholestatic liver disease was associated with unique pathways, suggesting it may drive disease pathogenesis.

Original languageEnglish (US)
Pages (from-to)481-497
Number of pages17
Issue number8
StatePublished - Apr 2022


  • DNA methylation
  • alcoholic liver disease
  • alcoholic steatohepatitis
  • cirrhosis
  • differentially methylated regions
  • epigenetic
  • methylome
  • primary biliary cholangitis
  • primary biliary cirrhosis
  • primary sclerosing cholangitis

ASJC Scopus subject areas

  • Genetics
  • Cancer Research


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