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

Nat Genet. 2011 Mar 13;43(4):329-32. doi: 10.1038/ng.789.


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). We followed up 28 loci in an additional UK cohort of 620 PBC cases and 2,514 population controls. We identified 12 new susceptibility loci (at a genome-wide significance level of P < 5 × 10⁻⁸) and replicated all previously associated loci. We identified three further new loci in a 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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / genetics
  • B7-1 Antigen / genetics
  • Case-Control Studies
  • Cohort Studies
  • Databases, Genetic
  • Death Domain Receptor Signaling Adaptor Proteins / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Guanine Nucleotide Exchange Factors / genetics
  • Humans
  • Immunity, Innate / genetics
  • Lectins, C-Type / genetics
  • Linkage Disequilibrium
  • Liver Cirrhosis, Biliary / genetics*
  • Liver Cirrhosis, Biliary / immunology
  • Male
  • Monosaccharide Transport Proteins / genetics
  • NF-kappa B p50 Subunit / genetics
  • Polymorphism, Single Nucleotide
  • Receptors, CXCR5 / genetics
  • Receptors, Interleukin-7 / genetics
  • Receptors, Tumor Necrosis Factor, Type I / genetics
  • Risk Factors
  • STAT4 Transcription Factor / genetics


  • B7-1 Antigen
  • CLEC16A protein, human
  • CXCR5 protein, human
  • DENND1B protein, human
  • Death Domain Receptor Signaling Adaptor Proteins
  • Guanine Nucleotide Exchange Factors
  • Lectins, C-Type
  • Monosaccharide Transport Proteins
  • NF-kappa B p50 Subunit
  • NFKB1 protein, human
  • Receptors, CXCR5
  • Receptors, Interleukin-7
  • Receptors, Tumor Necrosis Factor, Type I
  • STAT4 Transcription Factor
  • STAT4 protein, human
  • TNFRSF1A protein, human