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

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.

• Authors: Xingnan Li, Timothy D Howard, Siqun L Zheng, Tmirah Haselkorn, Stephen P Peters, Deborah A Meyers, Eugene R Bleecker
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 125 Issue 2 Pg. 328-335.e11 (Feb 2010) ISSN: 1097-6825 [Electronic] United States
• PMID: 20159242 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Chemical References

• DNA-Binding Proteins
• HLA-DQ Antigens
• HLA-DR Antigens
• Interleukin-13
• Acid Anhydride Hydrolases
• RAD50 protein, human
• DNA Repair Enzymes

Topics

• Acid Anhydride Hydrolases
• Adult
• Asthma (genetics)
• DNA Repair Enzymes (genetics)
• DNA-Binding Proteins (genetics)
• Female
• Genetic Predisposition to Disease (genetics)
• Genome-Wide Association Study
• Genotype
• HLA-DQ Antigens (genetics)
• HLA-DR Antigens (genetics)
• Humans
• Interleukin-13 (genetics)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide