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

Authors

  • J. Lasky-Su,

    1. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
    2. Center for Genomic Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
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    • These authors contributed equally to this manuscript.
  • B. E. Himes,

    1. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
    2. Partners Center for Personalized Genetic Medicine, Partners Health Care, Boston, MA, USA
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    • These authors contributed equally to this manuscript.
  • B. A. Raby,

    1. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
    2. Center for Genomic Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
    3. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
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  • B. J. Klanderman,

    1. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
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  • J. Senter Sylvia,

    1. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
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  • C. Lange,

    1. Center for Genomic Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
    2. Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA
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  • E. Melen,

    1. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
    2. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
    3. Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden
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  • F. D. Martinez,

    1. Respiratory Sciences Center, University of Arizona, Tuscon, AZ, USA
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  • E. Israel,

    1. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
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  • J. Gauderman,

    1. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
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  • F. Gilliland,

    1. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
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  • P. Sleiman,

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

    1. The Joseph Stokes Jr. Research Institute, The Children's Hospital of Philadelphia, Philadelphia, PA, USA
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  • J. C. Celedón,

    1. Division of Pediatric Pulmonary Medicine, Allergy and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
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  • M. Soto-Quiros,

    1. Division of Pediatric Pulmonology, Hospital Nacional de Niños, San José, Costa Rica
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  • L. Avila,

    1. Division of Pediatric Pulmonology, Hospital Nacional de Niños, San José, Costa Rica
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  • J. J. Lima,

    1. Nemours Children's Clinic, Centers for Clinical Pediatric Pharmacology & Pharmacogenetics, Jacksonville, FL, USA
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  • C. G. Irvin,

    1. Vermont Lung Center, Department of Medicine and Physiology, University of Vermont, Burlington, VT, USA
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  • S. P. Peters,

    1. 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
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  • H. Boushey,

    1. Division of Pulmonary/Critical Care and Allergy/Immunology, Department of Medicine, University of California at San Francisco, San Francisco, CA, USA
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  • V. M. Chinchilli,

    1. Department of Biostatistics, Penn State College of Medicine, Hershey, PA, USA
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  • D. Mauger,

    1. Department of Biostatistics, Penn State College of Medicine, Hershey, PA, USA
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  • K. Tantisira,

    1. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
    2. Center for Genomic Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
    3. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
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  • S. T. Weiss,

    Corresponding author
    1. Center for Genomic Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
    2. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
    3. Partners Center for Personalized Genetic Medicine, Partners Health Care, Boston, MA, USA
    • Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
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  • and for the SHARP investigators


Correspondence:

Scott T. Weiss, Channing Laboratory, Brigham and Women's Hospital

Boston, MA 02115, USA.

E-mail: scott.weiss@channing.harvard.edu

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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