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

Abstract

<jats:title>Abstract</jats:title><jats:p>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 (<jats:italic>n</jats:italic>=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (<jats:italic>n</jats:italic>=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (<jats:italic>P</jats:italic><jats:sub>combined</jats:sub>&lt;5 × 10<jats:sup>−8</jats:sup>) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine–cytokine pathways, for which relevant therapies exist.</jats:p>