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Genome-wide association study of asthma identifies RAD50-IL13 and HLA-DR/DQ regions

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Li, Xingnan, Howard, Timothy D., Zheng, Siqun L., Haselkorn, Tmirah, Peters, Stephen P., Meyers, Deborah A., Bleecker, Eugene R.·2010·Journal of Allergy and Clinical Immunology

Abstract

Background Asthma is a heterogeneous disease that is caused by the interaction of genetic susceptibility with environmental influences. Genome-wide association studies (GWAS) represent a powerful approach to investigate the association of DNA variants with disease susceptibility. To date, few GWAS for asthma have been reported. Objectives GWAS was performed on a population of severe or difficult-to-treat asthmatics to identify genes that are involved in the pathogenesis of asthma. Methods 292,443 SNPs were tested for association with asthma in 473 TENOR cases and 1,892 Illumina general population controls. Asthma-related quantitative traits (total serum IgE, FEV1, FVC, and FEV1/FVC) were also tested in identified candidate regions in 473 TENOR cases and 363 phenotyped controls without a history of asthma to further analyze GWAS results. Imputation was performed in identified candidate regions for analysis with denser SNP coverage. Results Multiple SNPs in the RAD50-IL13 region on chromosome 5q31.1 were associated with asthma: rs2244012 in intron 2 of RAD50 (P = 3.04E-07). The HLA-DR/DQ region on chromosome 6p21.3 was also associated with asthma: rs1063355 in the 3’ UTR of HLA-DQB1 (P = 9.55E-06). Imputation identified several significant SNPs in the TH2 locus control region (LCR) 3’ of RAD50. Imputation also identified a more significant SNP, rs3998159 (P = 1.45E-06), between HLA-DQB1 and HLA-DQA2. Conclusion This GWAS confirmed the important role of TH2 cytokine and antigen presentation genes in asthma at a genome-wide level and the importance of additional investigation of these two regions to delineate their structural complexity and biologic function in the development of asthma.

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Metadata

Authors
Li, X., Howard, T. D., Zheng, S. L., Haselkorn, T., Peters, S. P., Meyers, D. A., & Bleecker, E. R.
Venue
Journal of Allergy and Clinical Immunology
Publisher
Elsevier BV
Published
2010-02
Volume
125
Issue
2
Pages
328-335.e11
ISSN
0091-6749 (ISSN-L)
OpenAlex
W2159556553
Cited by
318
References
6
FWCI
25.87
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Genome-wide association study of asthma identifies RAD50-IL13 and HLA-DR/DQ regions. https://app.cochat.ai/papers/10.1016/j.jaci.2009.11.018
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Li, X., Howard, T. D., Zheng, S. L., Haselkorn, T., Peters, S. P., Meyers, D. A., & Bleecker, E. R. (2010). Genome-wide association study of asthma identifies RAD50-IL13 and HLA-DR/DQ regions. Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2009.11.018

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