Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease.

TitelGenome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease.
MedientypJournal Article
Jahr der Veröffentlichung2017
AutorenJi S-G, Juran BD, Mucha S, Folseraas T, Jostins L, Melum E, Kumasaka N, Atkinson EJ, Schlicht EM, Liu JZ, Shah T, Gutierrez-Achury J, Boberg KM, Bergquist A, Vermeire S, Eksteen B, Durie PR, Farkkila M, Müller T, Schramm C, Sterneck M, Weismüller TJ, Gotthardt DN, Ellinghaus D, Braun F, Teufel A, Laudes M, Lieb W, Jacobs G, Beuers U, Weersma RK, Wijmenga C, Marschall H-U, Milkiewicz P, Pares A, Kontula K, Chazouillères O, Invernizzi P, Goode E, Spiess K, Moore C, Sambrook J, Ouwehand WH, Roberts DJ, Danesh J, Floreani A, Gulamhusein AF, Eaton JE, Schreiber S, Coltescu C, Bowlus CL, Luketic VA, Odin JA, Chopra KB, Kowdley KV, Chalasani N, Manns MP, Srivastava B, Mells G, Sandford RN, Alexander G, Gaffney DJ, Chapman RW, Hirschfield GM, de Andrade M, Rushbrook SM, Franke A, Karlsen TH, Lazaridis KN, Anderson CA
Corporate AuthorsUK-PSC Consortium, International IBD Genetics Consortium, International PSC Study Group
JournalNat Genet
Datum der Veröffentlichung2017 Feb
SchlüsselwörterAdaptor Proteins, Signal Transducing, Alleles, Cholangitis, Sclerosing, Colitis, Ulcerative, Genome-Wide Association Study, Humans, Inflammatory Bowel Diseases, Polymorphism, Single Nucleotide, Risk Factors, RNA, Messenger

<p>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 (r) between PSC and ulcerative colitis (UC) (r= 0.29) was significantly greater than that between PSC and Crohn's disease (CD) (r= 0.04) (P = 2.55 × 10). UC and CD were genetically more similar to each other (r= 0.56) than either was to PSC (P < 1.0 × 10). Our study represents a substantial advance in understanding of the genetics of PSC.</p>

Alternate JournalNat. Genet.
PubMed ID27992413
PubMed Central IDPMC5540332
Grant ListRC4 AG039029 / AG / NIA NIH HHS / United States
RP-PG-0310-1002 / / Department of Health / United Kingdom
U01 AG009740 / AG / NIA NIH HHS / United States
R01 DK084960 / DK / NIDDK NIH HHS / United States
MC_PC_15018 / / Medical Research Council / United Kingdom
RP-PG-0310-1004 / / Department of Health / United Kingdom
RG/09/012/28096 / / British Heart Foundation / United Kingdom
RC2 AG036495 / AG / NIA NIH HHS / United States
/ / Wellcome Trust / United Kingdom