Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis

In addition to the HLA-locus, six genetic risk factors for primary biliary cirrhosis (PBC) have been identified in recent genome-wide association studies (GWAS). To identify additional loci, we carried out a GWAS using 1,840 cases from the UK PBC Consortium and 5,163 UK population controls as part of the Wellcome Trust Case Control Consortium 3 (WTCCC3). Twenty-eight loci were followed up in an additional UK cohort of 620 PBC cases and 2,514 population controls. We identified 12 novel risk loci (P<5×10(−8)) and replicated all previously associated loci. Three further novel loci were identified by meta-analysis of data from our study and previously published GWAS results. New candidate genes include STAT4, DENND1B, CD80, IL7R, CXCR5, TNFRSF1A, CLEC16A, and NFKB1. This study has considerably expanded our knowledge of the genetic architecture of PBC.