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Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects ( n =2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort ( n =3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC ( P  combined <5 × 10 −8 ) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine–cytokine pathways, for which relevant therapies exist.

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways