International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways
Abstract
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 (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined <5 × 10-8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.Citation
Cordell, H., Han, Y., Mells, G. et al. International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways. Nature Communications, 6, 8019 (2015). https://doi.org/10.1038/ncomms9019Publisher
SpringerJournal
Nature CommunicationsPubMed ID
26394269 (pubmed)Additional Links
https://www.nature.com/articles/ncomms9019Type
Journal articleLanguage
enDescription
© 2015 The Authors. Published by Springer. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1038/ncomms9019EISSN
2041-1723Sponsors
This study was funded by the Isaac Newton Trust, PBC Foundation, Medical Research Council (grant reference MR/L001489/1), Wellcome Trust (grants 085925), Ontario Physician Services Inc., Canadian Institutes for Health Research (MOP74621), the Ontario Research Fund (RE01-061) and National Institutes of Health (R01DK091823 and RO1DK80670). H.J.C. is a Wellcome Trust Research Fellow in the Basic Biomedical Science (087436 and 102858). C.S.G. is a Moore Investigator in Data-Driven Discovery (GBMF4552) and was supported in part by GM103534. G.F.M. is a post-doctoral clinical fellow of the National Institute for Health Research Rare Diseases (NIHR-RD) initiative. R.N.S. and G.M.H. receive salary support from a MRC-stratified medicine award (UK-PBC). C.I.A. is partially supported by P30 CA023108. K.A.S. is supported by the Sherman Family Chair in Genomic Medicine and a Canada Research Chair award. This study makes use of data generated by the WTCCC2 and WTCCC3, funded by the Wellcome Trust under awards 085475 and 090355. Access to genotype data from the TwinsUK cohort was kindly provided by the Department of Twin Research and Genetic Epidemiology at King’s College London. TwinsUK is funded by the Wellcome Trust and the European Community’s Seventh Framework Programme (FP7/2007-2013) and also receives support from the UK Department of Health via a National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre award to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London.Scopus Count
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Except where otherwise noted, this item's license is described as Licence for published version: Creative Commons Attribution 4.0 International