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Original Article

HLA-DQ strikes again: Genome-wide association study further confirms HLA-DQ in the diagnosis of asthma among adults

  1. J. Lasky-Su1,2,†,
  2. B. E. Himes1,17,†,
  3. B. A. Raby1,2,3,
  4. B. J. Klanderman1,
  5. J. Senter Sylvia1,
  6. C. Lange2,4,
  7. E. Melen1,5,6,
  8. F. D. Martinez7,
  9. E. Israel3,
  10. J. Gauderman8,
  11. F. Gilliland8,
  12. P. Sleiman9,
  13. H. Hakonarson9,
  14. J. C. Celedón10,
  15. M. Soto-Quiros11,
  16. L. Avila11,
  17. J. J. Lima12,
  18. C. G. Irvin13,
  19. S. P. Peters14,
  20. H. Boushey15,
  21. V. M. Chinchilli16,
  22. D. Mauger16,
  23. K. Tantisira1,2,3,
  24. S. T. Weiss1,2,3,17,*,
  25. and for the SHARP investigators

Article first published online: 26 NOV 2012

DOI: 10.1111/cea.12000

Issue

Clinical & Experimental Allergy

Clinical & Experimental Allergy

Volume 42, Issue 12, pages 1724–1733, December 2012

Additional Information

How to Cite

Cite this as: J. Lasky-Su , B. E. Himes , B. A. Raby , B. J. Klanderman , J. Senter Sylvia , C. Lange , E. Melen , F. D. Martinez , E. Israel , J. Gauderman , F. Gilliland , P. Sleiman , H. Hakonarson , J. C. Celedón , M. Soto-Quiros , L. Avila , J. J. Lima , C. G. Irvin , S. P. Peters , H. Boushey , V. M. Chinchilli , D. Mauger , K. Tantisira, S. T. Weiss and for the SHARP investigators, Clinical & Experimental Allergy 2012 (42) 1724–1733.

Author Information

  1. 1

    Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA

  2. 2

    Center for Genomic Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA

  3. 3

    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA

  4. 4

    Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA

  5. 5

    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

  6. 6

    Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden

  7. 7

    Respiratory Sciences Center, University of Arizona, Tuscon, AZ, USA

  8. 8

    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

  9. 9

    The Joseph Stokes Jr. Research Institute, The Children's Hospital of Philadelphia, Philadelphia, PA, USA

  10. 10

    Division of Pediatric Pulmonary Medicine, Allergy and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

  11. 11

    Division of Pediatric Pulmonology, Hospital Nacional de Niños, San José, Costa Rica

  12. 12

    Nemours Children's Clinic, Centers for Clinical Pediatric Pharmacology & Pharmacogenetics, Jacksonville, FL, USA

  13. 13

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

  14. 14

    Center for Genomics and Personalized Medicine Research, Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest University School of Medicine, Winston Salem, NC, USA

  15. 15

    Division of Pulmonary/Critical Care and Allergy/Immunology, Department of Medicine, University of California at San Francisco, San Francisco, CA, USA

  16. 16

    Department of Biostatistics, Penn State College of Medicine, Hershey, PA, USA

  17. 17

    Partners Center for Personalized Genetic Medicine, Partners Health Care, Boston, MA, USA

  1. †

    These authors contributed equally to this manuscript.

* Correspondence:
Scott T. Weiss, Channing Laboratory, Brigham and Women's Hospital
Boston, MA 02115, USA.
E-mail: scott.weiss@channing.harvard.edu

  1. †

    These authors contributed equally to this manuscript.

Publication History

  1. Issue published online: 26 NOV 2012
  2. Article first published online: 26 NOV 2012
  3. Accepted manuscript online: 28 AUG 2012 09:15AM EST
  4. Manuscript Accepted: 31 MAY 2012
  5. Manuscript Revised: 24 APR 2012
  6. Manuscript Received: 31 JAN 2012

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Summary

Background

Asthma is a common chronic respiratory disease in children and adults. An important genetic component to asthma susceptibility has long been recognized, most recently through the identification of several genes (e.g., ORMDL3, PDE4D, HLA-DQ, and TLE4) via genome-wide association studies.

Objective

To identify genetic variants associated with asthma affection status using genome-wide association data.

Methods

We describe results from a genome-wide association study on asthma performed in 3855 subjects using a panel of 455 089 single nucleotide polymorphisms (SNPs).

Result

The genome-wide association study resulted in the prioritization of 33 variants for immediate follow-up in a multi-staged replication effort. Of these, a common polymorphism (rs9272346) localizing to within 1 Kb of HLA-DQA1 (chromosome 6p21.3) was associated with asthma in adults (P-value = 2.2E-08) with consistent evidence in the more heterogeneous group of adults and children (P-value = 1.0E-04). Moreover, some genes identified in prior asthma GWAS were nominally associated with asthma in our populations.

Conclusion

Overall, our findings further replicate the HLA-DQ region in the pathogenesis of asthma. HLA-DQA1 is the fourth member of the HLA family found to be associated with asthma, in addition to the previously identified HLA-DRA, HLA-DQB1 and HLA-DQA2.

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