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

George F Mells, James A B Floyd, Katherine I Morley, Heather J Cordell, Christopher S Franklin, So-Youn Shin, Michael A Heneghan, James M Neuberger, Peter T Donaldson, Darren B Day, Samantha J Ducker, Agnes W Muriithi, Elizabeth F Wheater, Christopher J Hammond, Muhammad F Dawwas, David E Jones, Leena Peltonen, Graeme J Alexander, Richard N Sandford, Carl A AndersonUK PBC Consortium

Research output: Contribution to journalArticle (Academic Journal)peer-review

340 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)329-32
Number of pages4
JournalNature Genetics
Volume43
Issue number4
DOIs
Publication statusPublished - Apr 2011

Keywords

  • NF-kappa B p50 Subunit
  • Antigens, CD80
  • Polymorphism, Single Nucleotide
  • Adaptive Immunity
  • Receptors, Tumor Necrosis Factor, Type I
  • Humans
  • Immunity, Innate
  • Linkage Disequilibrium
  • Receptors, Interleukin-7
  • STAT4 Transcription Factor
  • Genome-Wide Association Study
  • Guanine Nucleotide Exchange Factors
  • Receptors, CXCR5
  • Death Domain Receptor Signaling Adaptor Proteins
  • Lectins, C-Type
  • Risk Factors
  • Cohort Studies
  • Case-Control Studies
  • Databases, Genetic
  • Genetic Predisposition to Disease
  • Liver Cirrhosis, Biliary
  • Monosaccharide Transport Proteins
  • Male
  • Female

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