Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis

Jimmy Z Liu, Mohamed A Almarri, Daniel J Gaffney, George F Mells, Luke Jostins, Heather J Cordell, Samantha J Ducker, Darren B Day, Michael A Heneghan, James M Neuberger, Peter T Donaldson, Andrew J Bathgate, Andrew Burroughs, Mervyn H Davies, David E Jones, Graeme J Alexander, Jeffrey C Barrett, Richard N Sandford, Carl A Anderson, The UK Primary Biliary Cirrhosis (PBC) ConsortiumAlexander Maxwell

Research output: Contribution to journalArticlepeer-review

171 Citations (Scopus)


We genotyped 2,861 cases of primary biliary cirrhosis (PBC) from the UK PBC Consortium and 8,514 UK population controls across 196,524 variants within 186 known autoimmune risk loci. We identified 3 loci newly associated with PBC (at P <5 × 10(-8)), increasing the number of known susceptibility loci to 25. The most associated variant at 19p12 is a low-frequency nonsynonymous SNP in TYK2, further implicating JAK-STAT and cytokine signaling in disease pathogenesis. An additional five loci contained nonsynonymous variants in high linkage disequilibrium (LD; r(2) > 0.8) with the most associated variant at the locus. We found multiple independent common, low-frequency and rare variant association signals at five loci. Of the 26 independent non-human leukocyte antigen (HLA) signals tagged on the Immunochip, 15 have SNPs in B-lymphoblastoid open chromatin regions in high LD (r(2) > 0.8) with the most associated variant. This study shows how data from dense fine-mapping arrays coupled with functional genomic data can be used to identify candidate causal variants for functional follow-up.
Original languageEnglish
Pages (from-to)1137-1141
Number of pages5
JournalNature Genetics
Issue number10
Publication statusPublished - Oct 2012

Bibliographical note

WTCCC3 management committee member

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis'. Together they form a unique fingerprint.

Cite this