Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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


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.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type



Prices may be subject to local taxes which are calculated during checkout

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.

Similar content being viewed by others


  1. Barnes, P.J. Immunology of asthma and chronic obstructive pulmonary disease. Nat. Rev. Immunol. 8, 183–192 (2008).

    Article  CAS  Google Scholar 

  2. Vercelli, D. Discovering susceptibility genes for asthma and allergy. Nat. Rev. Immunol. 8, 169–182 (2008).

    Article  CAS  Google Scholar 

  3. Kabesch, M. Novel asthma-associated genes from genome-wide association studies: what is their significance? Chest 137, 909–915 (2010).

    Article  CAS  Google Scholar 

  4. Moffatt, M.F. et al. Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature 448, 470–473 (2007).

    Article  CAS  Google Scholar 

  5. Himes, B.E. et al. Genome-wide association analysis identifies PDE4D as an asthma-susceptibility gene. Am. J. Hum. Genet. 84, 581–593 (2009).

    Article  CAS  Google Scholar 

  6. Sleiman, P.M. et al. Variants of DENND1B associated with asthma in children. N. Engl. J. Med. 362, 36–44 (2010).

    Article  CAS  Google Scholar 

  7. Li, X. et al. Genome-wide association study of asthma identifies RAD50-IL13 and HLA-DR/DQ regions. J. Allergy Clin. Immunol. 125, 328–335 (2010).

    Article  CAS  Google Scholar 

  8. Mathias, R.A. et al. A genome-wide association study on African-ancestry populations for asthma. J. Allergy Clin. Immunol. 125, 336–346 (2010).

    Article  CAS  Google Scholar 

  9. Moffatt, M.F. et al. A large-scale, consortium-based genomewide association study of asthma. N. Engl. J. Med. 363, 1211–1221 (2010).

    Article  CAS  Google Scholar 

  10. He, J.Q. et al. A thymic stromal lymphopoietin gene variant is associated with asthma and airway hyperresponsiveness. J. Allergy Clin. Immunol. 124, 222–229 (2009).

    Article  CAS  Google Scholar 

  11. Moffatt, M.F. et al. Association between quantitative traits underlying asthma and the HLA-DRB1 locus in a family-based population sample. Eur. J. Hum. Genet. 9, 341–346 (2001).

    Article  CAS  Google Scholar 

  12. Repapi, E. et al. Genome-wide association study identifies five loci associated with lung function. Nat. Genet. 42, 36–44 (2010).

    Article  CAS  Google Scholar 

  13. Hancock, D.B. et al. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function. Nat. Genet. 42, 45–52 (2010).

    Article  CAS  Google Scholar 

  14. Weiss, S.T. Lung function and airway diseases. Nat. Genet. 42, 14–16 (2010).

    Article  CAS  Google Scholar 

  15. Ziegler, S.F. & Artis, D. Sensing the outside world: TSLP regulates barrier immunity. Nat. Immunol. 11, 289–293 (2010).

    Article  CAS  Google Scholar 

  16. Ho, I.C. et al. GATA3 and the T-cell lineage: essential functions before and after T-helper-2-cell differentiation. Nat. Rev. Immunol. 9, 125–135 (2009).

    Article  CAS  Google Scholar 

  17. Wasserman, N.F. et al. An 8q24 gene desert variant associated with prostate cancer risk confers differential in vivo activity to a MYC enhancer. Genome Res. 20, 1191–1197 (2010).

    Article  CAS  Google Scholar 

  18. Hakonarson, H. et al. A novel susceptibility locus for type 1 diabetes on Chr12q13 identified by a genome-wide association study. Diabetes 57, 1143–1146 (2008).

    Article  CAS  Google Scholar 

  19. Petukhova, L. et al. Genome-wide association study in alopecia areata implicates both innate and adaptive immunity. Nature 466, 113–117 (2010).

    Article  CAS  Google Scholar 

  20. Pan, F. et al. Eos mediates Foxp3-dependent gene silencing in CD4+ regulatory T cells. Science 325, 1142–1146 (2009).

    Article  CAS  Google Scholar 

  21. Lambrecht, B.N. & Hammad, H. The role of dendritic and epithelial cells as master regulators of allergic airway inflammation. Lancet 376, 835–843 (2010).

    Article  CAS  Google Scholar 

  22. Sármay, G. et al. The multiple function of Grb2 associated binder (Gab) adaptor/scaffolding protein in immune cell signaling. Immunol. Lett. 104, 76–82 (2006).

    Article  Google Scholar 

  23. Harada, M. et al. A functional polymorphism in IL-18 is associated with severity of bronchial asthma. Am. J. Respir. Crit. Care Med. 180, 1048–1055 (2009).

    Article  CAS  Google Scholar 

  24. Nakamura, Y. The BioBank Japan Project. Clin. Adv. Hematol. Oncol. 5, 696–697 (2007).

    Google Scholar 

  25. Takata, R. et al. Genome-wide association study identifies five new susceptibility loci for prostate cancer in the Japanese population. Nat. Genet. 42, 751–754 (2010).

    Article  CAS  Google Scholar 

  26. Silverman, E.S. et al. Transforming growth factor-beta1 promoter polymorphism C-509T is associated with asthma. Am. J. Respir. Crit. Care Med. 169, 214–219 (2004).

    Article  Google Scholar 

  27. Silverman, E.S. et al. Constitutive and cytokine-induced expression of the ETS transcription factor ESE-3 in the lung. Am. J. Respir. Cell Mol. Biol. 27, 697–704 (2002).

    Article  CAS  Google Scholar 

  28. Peters, S.P. et al. Randomized comparison of strategies for reducing treatment in mild persistent asthma. N. Engl. J. Med. 356, 2027–2039 (2007).

    Article  Google Scholar 

  29. Luca, D. et al. On the use of general control samples for genome-wide association studies: genetic matching highlights causal variants. Am. J. Hum. Genet. 82, 453–463 (2008).

    Article  CAS  Google Scholar 

  30. Purcell, S. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559–575 (2007).

    Article  CAS  Google Scholar 

  31. Purcell, S. et al. Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics 19, 149–150 (2003).

    Article  CAS  Google Scholar 

  32. Price, A.L. et al. Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 38, 904–909 (2006).

    Article  CAS  Google Scholar 

Download references


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.

Author information

Authors and Affiliations



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.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–3 and Supplementary Tables 1–5. (PDF 2910 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing