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Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population

Nature Genetics volume 43, pages 893–896 (2011)Cite this article

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Abstract

Bronchial asthma is a common inflammatory disease caused by the interaction of genetic and environmental factors1,2. Through a genome-wide association study and a replication study consisting of a total of 7,171 individuals with adult asthma (cases) and 27,912 controls in the Japanese population, we identified five loci associated with susceptibility to adult asthma. In addition to the major histocompatibility complex and TSLP-WDR36 loci previously reported, we identified three additional loci: a USP38-GAB1 locus on chromosome 4q31 (combined P = 1.87 × 10−12), a locus on chromosome 10p14 (P = 1.79 × 10−15) and a gene-rich region on chromosome 12q13 (P = 2.33 × 10−13). We observed the most significant association with adult asthma at rs404860 in the major histocompatiblity complex region (P = 4.07 × 10−23), which is close to rs2070600, a SNP previously reported for association with FEV1/FVC in genome-wide association studies for lung function. Our findings offer a better understanding of the genetic contribution to asthma susceptibility.

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Figure 1: Case-control association results and LD map of the MHC region.
Figure 2: Case-control association results and LD maps of the four candidate regions.

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Acknowledgements

We thank all the subjects for participating in the study and also thank the collaborating physicians for helping with sample collection. We are grateful to the members of BioBank Japan and the Rotary Club of Osaka-Midosuji District 2660 Rotary International in Japan for supporting our study. We thank M.T. Shimizu, H. Sekiguchi, A.I. Jodo, N. Kawaraichi and the technical staff of the Center for Genomic Medicine for providing technical assistance. This work was conducted as a part of the BioBank Japan Project supported by of Ministry of Education, Culture, Sports, Science and Technology, Japan. This work was also partly supported by grants from the Ministry of Health, Labour and Welfare, Japan. We acknowledge the American Lung Association (ALA) and the ALA's Asthma Clinical Research Centers investigators and research teams for use of Leukotriene Modifier or Corticosteroid Salmeterol (LOCCS) and Effectiveness of Low Dose Theophylline as an Add-on Treatment in Asthma (LODO) data, with additional funding from HL071394 and HL074755 from the National Heart, Lung, and Blood Institute and the Nemours Children's Clinic. GlaxoSmithKline supported the conduct of the LOCCS Trial by an unrestricted grant to the ALA. We acknowledge Sepracor, Inc. for use of the Asthma Trial data. C.G.I. was supported by grants from the US National Institutes of Health NCRR RR022675 and RR015557 as well as the ALA, Asthma Clinical Research Center award. S.P.P. serves as an advisor to the data coordinating center of the ALA Asthma Clinical Research Centers and served as the principal investigator of the LOCCS trial.

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Authors and Affiliations

  1. Laboratory for Respiratory Diseases, Center for Genomic Medicine, RIKEN, Yokohama, Kanagawa, Japan

    Tomomitsu Hirota, Kaori Tomita & Mayumi Tamari

  2. Laboratory for Statistical Analysis, Center for Genomic Medicine, RIKEN, Tokyo, Japan

    Atsushi Takahashi

  3. Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN, Yokohama, Kanagawa, Japan

    Michiaki Kubo

  4. Laboratory for Medical Informatics, Center for Genomic Medicine, RIKEN, Yokohama, Kanagawa, Japan

    Tatsuhiko Tsunoda

  5. Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Habikino, Osaka, Japan

    Satoru Doi

  6. Miyatake Asthma Clinic, Osaka, Japan

    Kimie Fujita & Akihiko Miyatake

  7. Nonprofit Organization (NPO) Japan Health Promotion Supporting Network, Wakayama, Japan

    Tadao Enomoto

  8. Miyagawa Clinic, Gifu, Japan

    Takehiko Miyagawa

  9. First Department of Internal Medicine, Showa University School of Medicine, Shinagawa, Tokyo, Japan

    Mitsuru Adachi

  10. Third Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan

    Hiroshi Tanaka

  11. Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Akio Niimi, Hisako Matsumoto & Isao Ito

  12. Division of Respiratory Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan

    Hironori Masuko, Tohru Sakamoto & Nobuyuki Hizawa

  13. National Clinical Research Center, National Hospital Organization, Sagamihara National Hospital, Kanagawa, Japan

    Masami Taniguchi

  14. Nemours Children's Clinic, Centers for Clinical Pediatric Pharmacology and Pharmacogenetics, Jacksonville, Florida, USA

    John J Lima

  15. Department of Medicine and Physiology, Vermont Lung Center, University of Vermont, Vermont, Burlington, USA

    Charles G Irvin

  16. Center for Human Genomics, Section of Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest University School of Medicine, Winston Salem, North Carolina, USA

    Stephen P Peters

  17. Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA

    Blanca E Himes, Augusto A Litonjua, Kelan G Tantisira & Scott T Weiss

  18. Laboratory for International Alliance, Center for Genomic Medicine, RIKEN, Yokohama, Kanagawa, Japan

    Naoyuki Kamatani

  19. Laboratory of Molecular Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Yusuke Nakamura

Authors
  1. Tomomitsu Hirota
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  29. Mayumi Tamari
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Contributions

T.H. and M. Tamari designed the study and drafted the manuscript. A.T. and T.T. analyzed the GWAS data. T.H., K.T. and M.K. performed the genotyping for the GWAS. S.D., K.F., A.M., T.E., T.M., M.A., H.T., A.N., H. Matsumoto, I.I., H. Masuko, T.S., N.H. and M. Taniguchi collected subjects and participated in the diagnostic evaluations. B.E.H., A.A.L., K.G.T., J.J.L., C.G.I., S.P.P. and S.T.W. conducted an association study in a non-Hispanic population of European ancestry. M. Tamari and S.T.W. wrote the manuscript. M.K., N.K. and Y.N. contributed to the overall GWAS study design.

Corresponding author

Correspondence to Mayumi Tamari.

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The authors declare no competing financial interests.

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Hirota, T., Takahashi, A., Kubo, M. et al. Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population. Nat Genet 43, 893–896 (2011). https://doi.org/10.1038/ng.887

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