Update on primary sclerosing cholangitis genetics

Curr Opin Gastroenterol. 2014 May;30(3):310-9. doi: 10.1097/MOG.0000000000000052.


Purpose of review: The pathogenesis of primary sclerosing cholangitis (PSC) involves heritable factors. This review summarizes the recent genetic studies and discusses the implications of identified risk loci.

Recent findings: A total of 16 PSC susceptibility loci have been identified in genome-wide association studies and related study designs. At least 33 additional loci are involved in what is increasingly acknowledged to represent a general pool of genetic risk loci for immune-mediated diseases. One important group of genes is part of well characterized immune pathways (e.g. interleukin 2 signaling), whereas for other loci the relationship to PSC pathophysiology is less evident. Importantly, the loci collectively account for only 7.3% of overall PSC liability, thus pointing to a large contribution from environmental factors to PSC development. The individual PSC risk genes cannot be interpreted within a simple cause-effect model used for monogenic traits, but need to be explored for their individual biological correlates, preferably in a disease context. To some extent, as exemplified for the human leukocyte antigen and FUT2 associations, genetic findings may guide the discovery of interacting and co-occuring environmental susceptibility factors.

Summary: Multiple PSC susceptibility loci are now available for exploration in experimental model systems and patient-centered research.

Publication types

  • Review

MeSH terms

  • Animals
  • Cholangitis, Sclerosing / genetics*
  • Disease Models, Animal
  • Genetic Pleiotropy
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Mice
  • Translational Medical Research / methods