title: Update on primary sclerosing cholangitis genetics.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Multiple PSC susceptibility loci are now available for exploration in experimental model systems and patient-centered research.
authors.affiliation: aDivision of Cancer Medicine, Surgery and Transplantation, Department of Transplantation Medicine, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet bDivision of Cancer Medicine, Surgery and Transplantation, K.G. Jebsen Inflammation Research Centre, Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo cDepartment of Clinical Medicine, University of Bergen, Bergen, Norway.
authors.forename: Eva K K
authors.initials: EK
authors.lastname: Henriksen
authors.forename: Espen
authors.initials: E
authors.lastname: Melum
authors.forename: Tom H
authors.initials: TH
authors.lastname: Karlsen
mesh_terms: D000818:Animals; D015209:Cholangitis, Sclerosing / Q000235:genetics*; D004195:Disease Models, Animal; D058685:Genetic Pleiotropy; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D051379:Mice; D057170:Translational Research, Biomedical / Q000379:methods