A lecture on the genetics of primary sclerosing cholangitis

Abstract

As a result of international collaborations and application of genome-wide association studies (GWAS), a number of susceptibility genes for primary sclerosing cholangitis (PSC) have been detected over the recent years. The genetic architecture of PSC resembles prototypical HLA-associated autoimmune diseases almost as much as that of inflammatory bowel disease. All susceptibility loci reported have previously been detected in other phenotypes in accordance with a paradigm where risk loci detected by GWAS are likely to represent broad phenotypic features like inflammation rather than disease-specific affections. The risk loci have opened up for mechanistic studies in relevant model systems that are likely to enhance understanding of PSC pathogenesis. This review aims to summarize the status and thinking on genetics of PSC as drawn from present data and a series of recent review articles. A particular emphasis will be put on future opportunities related to the incorporation of metagenomic data in the analysis.