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].

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

CARBONE, MARCO
2012

Abstract

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.
Articolo in rivista - Articolo scientifico
Case-Control Studies; Chromosome Mapping; Chromosomes, Human, Pair 19; Gene Frequency; Genetic Loci; Genome-Wide Association Study; Genotype; HLA Antigens; Humans; Linkage Disequilibrium; Liver Cirrhosis, Biliary; Polymorphism, Single Nucleotide; Proteins; Regression Analysis; Sequence Analysis, DNA; TYK2 Kinase; Genetic Predisposition to Disease; Genetics
English
1137
1141
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Carbone, M. on behalf of UK Primary Biliary Cirrhosis PBC C
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].
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
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/141310
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