Liu, JZ; Almarri, MA; Gaffney, DJ; Jostins, L; Barrett, JC; Anderson, CA; ... Davies, MH; + view all Liu, JZ; Almarri, MA; Gaffney, DJ; Jostins, L; Barrett, JC; Anderson, CA; Mells, GF; Day, DB; Sandford, RN; Alexander, GJ; Cordell, HJ; Ducker, SJ; Donaldson, PT; Jones, DE; Heneghan, MA; Neuberger, JM; Bathgate, AJ; Burroughs, A; Davies, MH; - view fewer (2012) Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis. Nature Genetics , 44 (10) 1137 - 1141. 10.1038/ng.2395.
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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), 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 > 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 > 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. © 2012 Nature America, Inc. All rights reserved.
|Title:||Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis|
|Open access status:||An open access version is available from UCL Discovery|
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