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

J. Lasky-Su, B. E. Himes, B. A. Raby, B. J. Klanderman, J. Senter Sylvia, C. Lange, E. Melen, Fernando 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. BousheyV. M. Chinchilli, D. Mauger, K. Tantisira, S. T. Weiss

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1724-1733
Number of pages10
JournalClinical and Experimental Allergy
Volume42
Issue number12
DOIs
StatePublished - Dec 2012

Fingerprint

HLA-DQ Antigens
Genome-Wide Association Study
Asthma
HLA-DR alpha-Chains
Genes
Single Nucleotide Polymorphism
Chronic Disease
Chromosomes
Genome

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Lasky-Su, J., Himes, B. E., Raby, B. A., Klanderman, B. J., Sylvia, J. S., Lange, C., ... Weiss, S. T. (2012). HLA-DQ strikes again: Genome-wide association study further confirms HLA-DQ in the diagnosis of asthma among adults. Clinical and Experimental Allergy, 42(12), 1724-1733. https://doi.org/10.1111/cea.12000

HLA-DQ strikes again : Genome-wide association study further confirms HLA-DQ in the diagnosis of asthma among adults. / Lasky-Su, J.; Himes, B. E.; Raby, B. A.; Klanderman, B. J.; Sylvia, J. Senter; Lange, C.; Melen, E.; Martinez, Fernando; Israel, E.; Gauderman, J.; Gilliland, F.; Sleiman, P.; Hakonarson, H.; Celedón, J. C.; Soto-Quiros, M.; Avila, L.; Lima, J. J.; Irvin, C. G.; Peters, S. P.; Boushey, H.; Chinchilli, V. M.; Mauger, D.; Tantisira, K.; Weiss, S. T.

In: Clinical and Experimental Allergy, Vol. 42, No. 12, 12.2012, p. 1724-1733.

Research output: Contribution to journalArticle

Lasky-Su, J, Himes, BE, Raby, BA, Klanderman, BJ, Sylvia, JS, Lange, C, Melen, E, Martinez, F, Israel, E, Gauderman, J, Gilliland, F, Sleiman, P, Hakonarson, H, Celedón, JC, Soto-Quiros, M, Avila, L, Lima, JJ, Irvin, CG, Peters, SP, Boushey, H, Chinchilli, VM, Mauger, D, Tantisira, K & Weiss, ST 2012, 'HLA-DQ strikes again: Genome-wide association study further confirms HLA-DQ in the diagnosis of asthma among adults', Clinical and Experimental Allergy, vol. 42, no. 12, pp. 1724-1733. https://doi.org/10.1111/cea.12000
Lasky-Su, J. ; Himes, B. E. ; Raby, B. A. ; Klanderman, B. J. ; Sylvia, J. Senter ; Lange, C. ; Melen, E. ; Martinez, Fernando ; Israel, E. ; Gauderman, J. ; Gilliland, F. ; Sleiman, P. ; Hakonarson, H. ; Celedón, J. C. ; Soto-Quiros, M. ; Avila, L. ; Lima, J. J. ; Irvin, C. G. ; Peters, S. P. ; Boushey, H. ; Chinchilli, V. M. ; Mauger, D. ; Tantisira, K. ; Weiss, S. T. / HLA-DQ strikes again : Genome-wide association study further confirms HLA-DQ in the diagnosis of asthma among adults. In: Clinical and Experimental Allergy. 2012 ; Vol. 42, No. 12. pp. 1724-1733.
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T2 - Genome-wide association study further confirms HLA-DQ in the diagnosis of asthma among adults

AU - Lasky-Su, J.

AU - Himes, B. E.

AU - Raby, B. A.

AU - Klanderman, B. J.

AU - Sylvia, J. Senter

AU - Lange, C.

AU - Melen, E.

AU - Martinez, Fernando

AU - Israel, E.

AU - Gauderman, J.

AU - Gilliland, F.

AU - Sleiman, P.

AU - Hakonarson, H.

AU - Celedón, J. C.

AU - Soto-Quiros, M.

AU - Avila, L.

AU - Lima, J. J.

AU - Irvin, C. G.

AU - Peters, S. P.

AU - Boushey, H.

AU - Chinchilli, V. M.

AU - Mauger, D.

AU - Tantisira, K.

AU - Weiss, S. T.

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N2 - 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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