Primary sclerosing cholangitis (PSC) is a rare progressive disorder leading to bile duct destruction; ∼75% of patients have comorbid inflammatory bowel disease (IBD). We undertook the largest genome-wide association study of PSC (4,796 cases and 19,955 population controls) and identified four new genome-wide significant loci. The most associated SNP at one locus affects splicing and expression of UBASH3A, with the protective allele (C) predicted to cause nonstop-mediated mRNA decay and lower expression of UBASH3A. Further analyses based on common variants suggested that the genome-wide genetic correlation (rG) between PSC and ulcerative colitis (UC) (rG = 0.29) was significantly greater than that between PSC and Crohn's disease (CD) (rG = 0.04) (P = 2.55 × 10-15). UC and CD were genetically more similar to each other (rG = 0.56) than either was to PSC (P < 1.0 × 10-15). Our study represents a substantial advance in understanding of the genetics of PSC
Ji, S., Juran, B., Mucha, S., Folseraas, T., Jostins, L., Melum, E., et al. (2017). Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease. NATURE GENETICS, 49(2), 269-273.
Citazione: | Ji, S., Juran, B., Mucha, S., Folseraas, T., Jostins, L., Melum, E., et al. (2017). Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease. NATURE GENETICS, 49(2), 269-273. |
Tipo: | Articolo in rivista - Articolo scientifico |
Carattere della pubblicazione: | Scientifica |
Presenza di un coautore afferente ad Istituzioni straniere: | Si |
Titolo: | Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease |
Autori: | Ji, S; Juran, B; Mucha, S; Folseraas, T; Jostins, L; Melum, E; Kumasaka, N; Atkinson, E; Schlicht, E; Liu, J; Shah, T; Gutierrez Achury, J; Boberg, K; Bergquist, A; Vermeire, S; Eksteen, B; Durie, P; Farkkila, M; Müller, T; Schramm, C; Sterneck, M; Weismüller, T; Gotthardt, D; Ellinghaus, D; Braun, F; Teufel, A; Laudes, M; Lieb, W; Jacobs, G; Beuers, U; Weersma, R; Wijmenga, C; Marschall, H; Milkiewicz, P; Pares, A; Kontula, K; Chazouillères, O; Invernizzi, P; Goode, E; Spiess, K; Moore, C; Sambrook, J; Ouwehand, W; Roberts, D; Danesh, J; Floreani, A; Gulamhusein, A; Eaton, J; Schreiber, S; Coltescu, C; Bowlus, C; Luketic, V; Odin, J; Chopra, K; Kowdley, K; Chalasani, N; Manns, M; Srivastava, B; Mells, G; Sandford, R; Alexander, G; Gaffney, D; Chapman, R; Hirschfield, G; de Andrade, M; Rushbrook, S; Franke, A; Karlsen, T; Lazaridis, K; Anderson, C |
Autori: | |
Data di pubblicazione: | 2017 |
Lingua: | English |
Rivista: | NATURE GENETICS |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1038/ng.3745 |
Appare nelle tipologie: | 01 - Articolo su rivista |