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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Li, Xingnan Howard, Timothy D. Zheng, Siqun L. Haselkorn, Tmirah Peters, Stephen P. Meyers, Deborah A. Bleecker, Eugene R. |
| Description | Country affiliation: United States Author Affiliation: Li X ( Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.) |
| Abstract | BACKGROUND: Asthma is a heterogeneous disease that is caused by the interaction of genetic susceptibility with environmental influences. Genome-wide association studies (GWASs) represent a powerful approach to investigate the association of DNA variants with disease susceptibility. To date, few GWASs for asthma have been reported. OBJECTIVES: A GWAS was performed on a population of patients with severe or difficult-to-treat asthma to identify genes that are involved in the pathogenesis of asthma. METHODS: A total of 292,443 single nucleotide polymorphisms (SNPs) were tested for association with asthma in 473 The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) cases and 1892 Illumina general population controls. Asthma-related quantitative traits (total serum IgE, FEV(1), forced vital capacity, and FEV(1)/forced vital capacity) were also tested in identified candidate regions in 473 TENOR cases and 363 phenotyped controls without a history of asthma to analyze GWAS results further. 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' untranslated region of HLA-DQB1 (P = 9.55E-06). Imputation identified several significant SNPs in the T(H)2 locus control region 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 T(H)2 cytokine and antigen presentation genes in asthma at a genome-wide level and the importance of additional investigation of these 2 regions to delineate their structural complexity and biologic function in the development of asthma. |
| File Format | HTM / HTML |
| ISSN | 00916749 |
| e-ISSN | 10976825 |
| DOI | 10.1016/j.jaci.2009.11.018 |
| Journal | Journal of Allergy and Clinical Immunology |
| Issue Number | 2 |
| Volume Number | 125 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2010-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Immunology Asthma Genetics Dna Repair Enzymes Dna-binding Proteins Genetic Predisposition To Disease Hla-dq Antigens Hla-dr Antigens Interleukin-13 Genome-wide Association Study Genotype Polymorphism, Single Nucleotide Multicenter Study Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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