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

• Letter
• Published: 15 November 2009
• 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

Nature Genetics volume 41, pages 1325–1329 (2009)Cite this article

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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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Acknowledgements

We thank all of the patients who participated in this study. We are grateful to F. Hirai, K. Aoyagi, T. Fuchigami, M. Miyazaki, S. Yada, M. Esaki, H. Koga, S. Nakamura, S. Motoya, M. Nomura and T. Sonoda for collecting samples. We thank R. Nakamichi and T. Morizono for help with statistical analysis; participants of the Midosuji and other related Rotary Clubs, Hisayama residents and staff of the Division of Health and Welfare of Hisayama for cooperation in this study; and K. Ashikawa, H. Amitani and other staff of the Laboratory for Genotyping Development, Center for Genomic Medicine, for contributions to this study. This work was supported in part by the Ministry of Education, Culture, Sports, Science and Technology.

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Authors and Affiliations

1. Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN, Yokohama Institute, Yokohama, Japan
   Kouichi Asano, Tomonaga Matsushita, Junji Umeno, Naoya Hosono & Michiaki Kubo
2. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
   Kouichi Asano, Tomonaga Matsushita, Junji Umeno, Takayuki Matsumoto, Mitsuo Iida & Michiaki Kubo
3. Department of Environmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
   Kouichi Asano, Yutaka Kiyohara & Michiaki Kubo
4. Laboratory for Statistical Analysis, Center for Genomic Medicine, RIKEN, Yokohama Institute, Japan
   Atsushi Takahashi & Naoyuki Kamatani
5. Laboratory for Medical Informatics, Center for Genomic Medicine, RIKEN, Yokohama Institute, Japan
   Takahisa Kawaguchi & Tatsuhiko Tsunoda
6. Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan
   Toshiyuki Matsui
7. Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
   Yoichi Kakuta, Yoshitaka Kinouchi & Tooru Shimosegawa
8. First Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
   Masayo Hosokawa, Yoshiaki Arimura & Yasuhisa Shinomura
9. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
   Yusuke Nakamura

Authors

1. Kouichi Asano
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2. Tomonaga Matsushita
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3. Junji Umeno
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4. Naoya Hosono
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5. Atsushi Takahashi
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6. Takahisa Kawaguchi
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7. Takayuki Matsumoto
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8. Toshiyuki Matsui
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9. Yoichi Kakuta
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10. Yoshitaka Kinouchi
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11. Tooru Shimosegawa
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12. Masayo Hosokawa
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13. Yoshiaki Arimura
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14. Yasuhisa Shinomura
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15. Yutaka Kiyohara
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16. Tatsuhiko Tsunoda
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17. Naoyuki Kamatani
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18. Mitsuo Iida
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19. Yusuke Nakamura
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20. Michiaki Kubo
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Contributions

Y.N., N.K., M.K. and K.A. designed the study. K.A., T. Matsushita and N.H. performed the genotyping. A.T., T.K., T.T. and N.K. performed the data analyses. J.U., T. Matsumoto, T. Matsui and Y. Kiyohara managed the DNA samples and clinical information of the GWAS. Y. Kakuta, Y. Kinouchi and T.S. performed the genotyping in the first replication study. M.H., Y.A. and Y.S. performed the genotyping in the second replication study. Y.N., M.K., J.U. and K.A. wrote the manuscript. M.I., Y.N. and M.K. supervised the study.

Corresponding author

Correspondence toMichiaki Kubo.

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Asano, K., Matsushita, T., Umeno, J. et al. A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population.Nat Genet 41, 1325–1329 (2009). https://doi.org/10.1038/ng.482

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• Received: 03 March 2009
• Accepted: 25 August 2009
• Published: 15 November 2009
• Issue Date: December 2009
• DOI: https://doi.org/10.1038/ng.482

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