Letter abstract


Nature Genetics 41, 1325 - 1329 (2009)
Published online: 15 November 2009 | doi:10.1038/ng.482

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

Kouichi Asano1,2,3, Tomonaga Matsushita1,2, Junji Umeno1,2, Naoya Hosono1, Atsushi Takahashi4, Takahisa Kawaguchi5, Takayuki Matsumoto2, Toshiyuki Matsui6, Yoichi Kakuta7, Yoshitaka Kinouchi7, Tooru Shimosegawa7, Masayo Hosokawa8, Yoshiaki Arimura8, Yasuhisa Shinomura8, Yutaka Kiyohara3, Tatsuhiko Tsunoda5, Naoyuki Kamatani4, Mitsuo Iida2, Yusuke Nakamura9 & Michiaki Kubo1,2,3

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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 times 10-12), a locus on chromosome 13q12 (rs17085007, P = 6.64 times 10-8) and the glycoprotein gene SLC26A3 (rs2108225, P = 9.50 times 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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  1. Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN, Yokohama Institute, Yokohama, Japan.
  2. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  3. Department of Environmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  4. Laboratory for Statistical Analysis, Center for Genomic Medicine, RIKEN, Yokohama Institute, Japan.
  5. Laboratory for Medical Informatics, Center for Genomic Medicine, RIKEN, Yokohama Institute, Japan.
  6. Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan.
  7. Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
  8. First Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
  9. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.

Correspondence to: Michiaki Kubo1,2,3 e-mail: mkubo@src.riken.jp