ICOS and primary biliary cholangitis: On the basis of the functional role of all the three genes in T-cell costimulatory pathways, the CD28-CTLA4-ICOS locus has long been suggested by many candidate gene studies as a PBC risk locus, but large-scale GWAS and dense fine-mapping studies in European PBC cohorts have not revealed this association2, 3, 4, 5, 6, 7.