Genetic Risk and the Development of Autoimmune Liver Disease

Dig Dis. 2015;33 Suppl 2:13-24. doi: 10.1159/000440706. Epub 2015 Dec 7.


Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) have collectively been recognized as autoimmune liver diseases. They have all been subjected to genome-wide association studies (GWAS) and several dozens susceptibility loci have been determined. The predominant feature of the genetic findings is that of a strong association with the human leukocyte antigen (HLA) and numerous weak associations scattered throughout the remainder of the genome. The non-HLA associations show some degree of overlap, not only between PBC, PSC and AIH, but also with other autoimmune and immune-mediated diseases. Mathematical modelling shows that the main fraction of autoimmune disease risk (including that of autoimmune liver diseases) is not explained by GWAS, proposing a major role of environmental factors. The HLA associations and autoantibodies observed in these conditions may hold clues as to the nature of such factors, which are exceedingly difficult to map by means of epidemiological study designs. The present review article explores the potential relationship between genetic risk as determined by GWAS and environmental risk in autoimmune liver diseases, and proposes a model for relevant thinking on the susceptibility genes in PBC, PSC and AIH.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cholangitis, Sclerosing / genetics*
  • Cholangitis, Sclerosing / immunology
  • Gene-Environment Interaction
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • HLA Antigens / immunology
  • Hepatitis, Autoimmune / genetics*
  • Hepatitis, Autoimmune / immunology
  • Humans
  • Liver Cirrhosis, Biliary / genetics*
  • Liver Cirrhosis, Biliary / immunology
  • Risk Factors


  • HLA Antigens