A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population

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

Research output: Contribution to journalArticle

158 Citations (Scopus)

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 × 10 12), a locus on chromosome 13q12 (rs17085007, P = 6.64 × 10 8) and the glycoprotein gene SLC26A3 (rs2108225, P = 9.50 × 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.

Original languageEnglish
Pages (from-to)1325-1329
Number of pages5
JournalNature Genetics
Volume41
Issue number12
DOIs
Publication statusPublished - 01-12-2009

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Genome-Wide Association Study
Ulcerative Colitis
Population
Immunoglobulin Genes
Disease Susceptibility
Major Histocompatibility Complex
Inflammatory Bowel Diseases
Genes
Autoimmune Diseases
Single Nucleotide Polymorphism
Glycoproteins
Immunoglobulin G
Chromosomes

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Asano, Kouichi ; Matsushita, Tomonaga ; Umeno, Junji ; Hosono, Naoya ; Takahashi, Atsushi ; Kawaguchi, Takahisa ; Matsumoto, Takayuki ; Matsui, Toshiyuki ; Kakuta, Yoichi ; Kinouchi, Yoshitaka ; Shimosegawa, Tooru ; Hosokawa, Masayo ; Arimura, Yoshiaki ; Shinomura, Yasuhisa ; Kiyohara, Yutaka ; Tsunoda, Tatsuhiko ; Kamatani, Naoyuki ; Iida, Mitsuo ; Nakamura, Yusuke ; Kubo, Michiaki. / A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population. In: Nature Genetics. 2009 ; Vol. 41, No. 12. pp. 1325-1329.
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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 × 10 12), a locus on chromosome 13q12 (rs17085007, P = 6.64 × 10 8) and the glycoprotein gene SLC26A3 (rs2108225, P = 9.50 × 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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Asano, K, Matsushita, T, Umeno, J, Hosono, N, Takahashi, A, Kawaguchi, T, Matsumoto, T, Matsui, T, Kakuta, Y, Kinouchi, Y, Shimosegawa, T, Hosokawa, M, Arimura, Y, Shinomura, Y, Kiyohara, Y, Tsunoda, T, Kamatani, N, Iida, M, Nakamura, Y & Kubo, M 2009, 'A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population', Nature Genetics, vol. 41, no. 12, pp. 1325-1329. https://doi.org/10.1038/ng.482

A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population. / Asano, Kouichi; Matsushita, Tomonaga; Umeno, Junji; Hosono, Naoya; Takahashi, Atsushi; Kawaguchi, Takahisa; Matsumoto, Takayuki; Matsui, Toshiyuki; Kakuta, Yoichi; Kinouchi, Yoshitaka; Shimosegawa, Tooru; Hosokawa, Masayo; Arimura, Yoshiaki; Shinomura, Yasuhisa; Kiyohara, Yutaka; Tsunoda, Tatsuhiko; Kamatani, Naoyuki; Iida, Mitsuo; Nakamura, Yusuke; Kubo, Michiaki.

In: Nature Genetics, Vol. 41, No. 12, 01.12.2009, p. 1325-1329.

Research output: Contribution to journalArticle

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T1 - A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population

AU - Asano, Kouichi

AU - Matsushita, Tomonaga

AU - Umeno, Junji

AU - Hosono, Naoya

AU - Takahashi, Atsushi

AU - Kawaguchi, Takahisa

AU - Matsumoto, Takayuki

AU - Matsui, Toshiyuki

AU - Kakuta, Yoichi

AU - Kinouchi, Yoshitaka

AU - Shimosegawa, Tooru

AU - Hosokawa, Masayo

AU - Arimura, Yoshiaki

AU - Shinomura, Yasuhisa

AU - Kiyohara, Yutaka

AU - Tsunoda, Tatsuhiko

AU - Kamatani, Naoyuki

AU - Iida, Mitsuo

AU - Nakamura, Yusuke

AU - Kubo, Michiaki

PY - 2009/12/1

Y1 - 2009/12/1

N2 - 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 × 10 12), a locus on chromosome 13q12 (rs17085007, P = 6.64 × 10 8) and the glycoprotein gene SLC26A3 (rs2108225, P = 9.50 × 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.

AB - 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 × 10 12), a locus on chromosome 13q12 (rs17085007, P = 6.64 × 10 8) and the glycoprotein gene SLC26A3 (rs2108225, P = 9.50 × 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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