Author information

• ¹Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy; Ancient DNA Lab, Dan David Center for Human Evolution and Biohistory Research, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: a.gerussi@campus.unimib.it.
• ²Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy.
• ³Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis (MIVB-H), French Network on Rare Liver Diseases (FILFOIE), Saint-Antoine Hospital, Assistance Publique - Hôpitaux de Paris, Sorbonne University, Paris, France; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Saint- Antoine Hospital, Paris, France.
• ⁴European Reference Network on Hepatological Diseases (ERN RARE-LIVER), I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany; Hamburg Center for Translational Immunology (HCTI), Hamburg, Germany.
• ⁵Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, 20072, Italy; IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Milan, Italy.
• ⁶Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy. Electronic address: pietro.invernizzi@unimib.it.

Abstract

Primary biliary cholangitis (PBC) is a rare autoimmune disease of the liver affecting the small bile ducts. From a genetic point of view, PBC is a complex trait and several genetic and environmental factors have been called in action to explain its etiopathogenesis. Similarly to other complex traits, PBC has benefited from the introduction of genome-wide association studies (GWAS), which identified many variants predisposing or protecting toward the development of the disease. While a progressive endeavour toward the characterization of candidate loci and downstream pathways is currently ongoing, there is still a relatively large portion of heritability of PBC to be revealed. In addition, genetic variation behind progression of the disease and therapeutic response are mostly to be investigated yet. This review outlines the state-of-the-art regarding the genetic architecture of PBC and provides some hints for future investigations, focusing on the study of gene-gene interactions, the application of whole-genome sequencing techniques, and the investigation of X chromosome that can be helpful to cover the missing heritability gap in PBC.