A Genome-wide Association Study Identifies Three New Susceptibility Loci for Ulcerative Colitis in the Japanese Population

Overview

Journal Nat Genet

Specialty Genetics

Date 2009 Nov 17

PMID 19915573

Citations 129

Authors

Kouichi Asano

Tomonaga Matsushita

Junji Umeno

Naoya Hosono

Atsushi Takahashi

Takahisa Kawaguchi

Takayuki Matsumoto

Toshiyuki Matsui

Yoichi Kakuta

Yoshitaka Kinouchi

Tooru Shimosegawa

Masayo Hosokawa

Yoshiaki Arimura

Yasuhisa Shinomura

Yutaka Kiyohara

Tatsuhiko Tsunoda

Naoyuki Kamatani

Mitsuo Iida

Yusuke Nakamura

Michiaki Kubo

Affiliations

Soon will be listed here.

Abstract

Ulcerative colitis is one of the principal forms of inflammatory bowel disease with complex manifestations. Although previous studies have indicated that there is a genetic contribution to the pathogenesis of ulcerative colitis, the genes influencing susceptibility to the disease have not been fully determined. To identify genetic factors conferring risk of ulcerative colitis, here we conducted a two-stage genome-wide association study and subsequent replication study using 1,384 Japanese individuals with ulcerative colitis and 3,057 control subjects. In addition to the expected strong association with the major histocompatibility complex (MHC) region, we identified three new susceptibility loci: the immunoglobulin receptor gene FCGR2A (rs1801274, P = 1.56 x 10(-12)), a locus on chromosome 13q12 (rs17085007, P = 6.64 x 10(-8)) and the glycoprotein gene SLC26A3 (rs2108225, P = 9.50 x 10(-8)). rs1801274 is a nonsynonymous SNP of FCGR2A that is reported to have a critical effect on receptor binding affinity for IgG and to be associated with other autoimmune diseases. Our findings provide insight into the molecular pathogenesis of ulcerative colitis.

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