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Genetics in PSC: What Do the “Risk Genes” Teach Us?

  • Trine Folseraas
  • Evaggelia Liaskou
  • Carl. A. Anderson
  • Tom H. KarlsenEmail author
Article

Abstract

A role of genetics in primary sclerosing cholangitis (PSC) development is now firmly established. A total of 16 risk genes have been reported at highly robust (“genome-wide”) significance levels, and ongoing efforts suggest that the list will ultimately be considerably longer. Importantly, this genetic risk pool so far accounts for less than 10 % of an estimated overall PSC susceptibility. The relative importance of genetic versus environmental factors (including gene-gene and gene-environment interactions) in remaining aspects of PSC pathogenesis is unknown, and other study designs than genome-wide association studies are needed to explore these aspects. For some of the loci, e.g. HLA and FUT2, distinct interacting environmental factors may exist, and working from the genetic associations may prove one valid path for determining the specific nature of environmental triggers. So far the biological implications for PSC risk genes are typically merely hypothesized based on previously published literature, and there is therefore a strong need for dedicated translational studies to determine their roles within the specific disease context of PSC. Apparently, most risk loci seem to involve in a subset of biological pathways for which genetic associations exist in a multitude of immune-mediated diseases, accounting for both inflammatory bowel disease as well as prototypical autoimmunity. In the present article, we will survey the current knowledge on PSC genetics with a particular emphasis on the pathophysiological insight potentially gained from genetic risk loci involving in this profound immunogenetic pleiotropy.

Keywords

Primary sclerosing cholangitis Genome-wide association study 

Notes

Acknowledgements

We thank Tor Halland (TorDesign) and Øystein Horgmo (University of Oslo) for assistance in preparing Fig. 1 and Fig. 2, respectively.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Trine Folseraas
    • 1
    • 2
  • Evaggelia Liaskou
    • 3
  • Carl. A. Anderson
    • 4
  • Tom H. Karlsen
    • 1
    • 2
    • 5
    Email author
  1. 1.Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and TransplantationOslo University Hospital RikshospitaletOsloNorway
  2. 2.K.G Jebsen Inflammation Research Centre, Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery and TransplantationOslo University Hospital RikshospitaletOsloNorway
  3. 3.Centre for Liver Research and NIHR Biomedical Research Unit, Institute of Biomedical ResearchUniversity of BirminghamBirminghamUK
  4. 4.Wellcome Trust Genome CampusWellcome Trust Sanger InstituteCambridgeUK
  5. 5.Department of Clinical MedicineUniversity of BergenBergenNorway

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