Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region.
Citation:
Barrett JC, Lee JC, Lees CW, Prescott NJ, Anderson CA, Phillips A, Wesley E, Parnell K, Zhang H, Drummond H, Nimmo ER, Massey D, Blaszczyk K, Elliott T, Cotterill L, Dallal H, Lobo AJ, Mowat C, Sanderson JD, Jewell DP, Newman WG, Edwards C, Ahmad T, Mansfield JC, Satsangi J, Parkes M, Mathew CG, Donnelly P, Peltonen L, Blackwell JM, Bramon E, Brown MA, Casas JP, Corvin A, Craddock N, Deloukas P, Duncanson A, Jankowski J, Markus HS, Mathew CG, McCarthy MI, Palmer CN, Plomin R, Rautanen A, Sawcer SJ, Samani N, Trembath RC, Viswanathan AC, Wood N, Spencer CC, Barrett JC, Bellenguez C, Davison D, Freeman C, Strange A, Donnelly P, Langford C, Hunt SE, Edkins S, Gwilliam R, Blackburn H, Bumpstead SJ, Dronov S, Gillman M, Gray E, Hammond N, Jayakumar A, McCann OT, Liddle J, Perez ML, Potter SC, Ravindrarajah R, Ricketts M, Waller M, Weston P, Widaa S, Whittaker P, Deloukas P, Peltonen L, Mathew CG, Blackwell JM, Brown MA, Corvin A, McCarthy MI, Spencer CC, Attwood AP, Stephens J, Sambrook J, Ouwehand WH, McArdle WL, Ring SM, Strachan DP, Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region., Nature Genetics, 41, 12, 2009, 1330-1334Download Item:
Abstract:
Ulcerative colitis (UC) is a common form of inflammatory bowel disease with a complex
aetiology. As part of the Wellcome Trust Case Control Consortium 2, we performed a genome-
wide association scan for UC in 2361 cases and 5417 controls. Loci showing evidence of
association at P < 1 ? 10
?5
were followed up by genotyping in an independent set of 2321 cases
and 4818 controls. We find genome-wide significant evidence of association at three new loci,
each containing at least one biologically relevant candidate gene, on chromosomes 20q13
(
HNF4A
; P = 3.2 ? 10
?17
), 16q22 (
CDH1
and
CDH3
; P = 2.8 ? 10
?8
) and 7q31 (
LAMB1
; 3.0 ?
10
?8
). Of note,
CDH1
has recently been associated with susceptibility to colorectal cancer, which
is an established complication of longstanding UC. The new associations suggest that changes in
the integrity of the intestinal epithelial barrier may contribute to the pathogenesis of UC
Sponsor
Grant Number
Wellcome Trust
Author's Homepage:
http://people.tcd.ie/acorvinDescription:
PUBLISHED
Author: CORVIN, AIDEN PETER
Type of material:
Journal ArticleCollections
Series/Report no:
Nature Genetics;41;
12;
Availability:
Full text availableKeywords:
Ulcerative colitisMetadata
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