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; r2 > 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. © 2012 Nature America, Inc. All rights reserved.
Liu, J., Almarri, M., Gaffney, D., Mells, G., Jostins, L., Cordell, H., et al. (2012). Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis. NATURE GENETICS, 44(10), 1137-1141 [10.1038/ng.2395].
Citazione: | Liu, J., Almarri, M., Gaffney, D., Mells, G., Jostins, L., Cordell, H., et al. (2012). Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis. NATURE GENETICS, 44(10), 1137-1141 [10.1038/ng.2395]. | |
Tipo: | Articolo in rivista - Articolo scientifico | |
Carattere della pubblicazione: | Scientifica | |
Presenza di un coautore afferente ad Istituzioni straniere: | Si | |
Titolo: | Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis | |
Autori: | Liu, J; Almarri, M; Gaffney, D; Mells, G; Jostins, L; Cordell, H; Ducker, S; Day, D; Heneghan, M; Neuberger, J; Donaldson, P; Bathgate, A; Burroughs, A; Davies, M; Jones, D; Alexander, G; Barrett, J; Sandford, R; Anderson, C; Carbone, M | |
Autori: | ||
Data di pubblicazione: | 2012 | |
Lingua: | English | |
Rivista: | NATURE GENETICS | |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1038/ng.2395 | |
Appare nelle tipologie: | 01 - Articolo su rivista |