Immunogenetics in primary sclerosing cholangitis

Brian Chung, Gideon Hirschfield

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)
251 Downloads (Pure)


Purpose of Review: Primary sclerosing cholangitis (PSC) is progressive biliary liver disorder strongly associated with inflammatory bowel disease (PSC-IBD). We summarize the genetics of PSC-IBD and highlight recent findings that further differentiate PSC-IBD as a unique disease.

Recent findings: To date, genome-wide studies have uncovered 23 susceptibility loci for PSC-IBD; the majority of which have been previously reported as risk factors in other immune-mediated disorders. For most candidates, the pathological relationship to PSC-IBD remains largely unknown. Several of candidate genes appear to be liver-related but the large majority relate to immunity and reaffirm that alterations to immune function, trafficking and tolerance are likely to influence susceptibility and presentation of PSC-IBD. Similar to most immune-mediated diseases, the strongest association in PSC-IBD resides within the human leukocyte antigen (HLA) complex and suggests that disease-specific antigens drive pathogenic immune responses. Although genetic predisposition influences disease, genetic determinants account for less than 10% of total disease liability in PSC-IBD, clearly emphasizing the predominant role of environmental factors on disease susceptibility.

Summary: Genetic studies define PSC-IBD as a unique disease to IBD mirroring clinical observations. Most risk loci harbour immune-related genes and disease variants are likely to perturb immune function, tolerance and/or trafficking. Additional studies in patients and novel experimental systems are needed to identify the origin and impact of environmental factors in relation to genetic predisposition in PSC-IBD.
Original languageEnglish
Pages (from-to)93-98
JournalCurrent Opinion in Gastroenterology
Issue number2
Publication statusPublished - Mar 2017


  • primary sclerosing cholangitis
  • inflammatory bowel disease
  • genome-wide association studies
  • autoimmunity
  • pleiotropy
  • microbiota


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