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. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
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. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Authors: T C van der Pouw Kraan; A van Veen; L C Boeije; S A van Tuyl; E R de Groot; S O Stapel; A Bakker; C L Verweij; L A Aarden; J S van der Zee Journal: Genes Immun Date: 1999-09 Impact factor: 2.676
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Authors: A Heinzmann; X Q Mao; M Akaiwa; R T Kreomer; P S Gao; K Ohshima; R Umeshita; Y Abe; S Braun; T Yamashita; M H Roberts; R Sugimoto; K Arima; Y Arinobu; B Yu; S Kruse; T Enomoto; Y Dake; M Kawai; S Shimazu; S Sasaki; C N Adra; M Kitaichi; H Inoue; K Yamauchi; N Tomichi; F Kurimoto; N Hamasaki; J M Hopkin; K Izuhara; T Shirakawa; K A Deichmann Journal: Hum Mol Genet Date: 2000-03-01 Impact factor: 6.150
Authors: Youming Zhang; Nicholas I Leaves; Gavin G Anderson; Chris P Ponting; John Broxholme; Richard Holt; Pauline Edser; Sumit Bhattacharyya; Andy Dunham; Ian M Adcock; Louise Pulleyn; Peter J Barnes; John I Harper; Gonçalo Abecasis; Lon Cardon; Melanie White; John Burton; Lucy Matthews; Richard Mott; Mark Ross; Roger Cox; Miriam F Moffatt; William O C M Cookson Journal: Nat Genet Date: 2003-06 Impact factor: 38.330
Authors: Paul Van Eerdewegh; Randall D Little; Josée Dupuis; Richard G Del Mastro; Kathy Falls; Jason Simon; Dana Torrey; Sunil Pandit; Joyce McKenny; Karen Braunschweiger; Alison Walsh; Ziying Liu; Brooke Hayward; Colleen Folz; Susan P Manning; Alicia Bawa; Lisa Saracino; Michelle Thackston; Youssef Benchekroun; Neva Capparell; Mei Wang; Ron Adair; Yun Feng; JoAnn Dubois; Michael G FitzGerald; Hui Huang; René Gibson; Kristina M Allen; Alex Pedan; Melvyn R Danzig; Shelby P Umland; Robert W Egan; Francis M Cuss; Steuart Rorke; Joanne B Clough; John W Holloway; Stephen T Holgate; Tim P Keith Journal: Nature Date: 2002-07-10 Impact factor: 49.962
Authors: Jared M Bischof; Christopher J Ott; Shih-Hsing Leir; Nehal Gosalia; Lingyun Song; Darin London; Terrence S Furey; Calvin U Cotton; Gregory E Crawford; Ann Harris Journal: Thorax Date: 2011-12-14 Impact factor: 9.139
Authors: Xingnan Li; Elizabeth J Ampleford; Timothy D Howard; Wendy C Moore; Huashi Li; William W Busse; Mario Castro; Serpil C Erzurum; Anne M Fitzpatrick; Benjamin Gaston; Elliot Israel; Nizar N Jarjour; W Gerald Teague; Sally E Wenzel; Gregory A Hawkins; Eugene R Bleecker; Deborah A Meyers Journal: J Allergy Clin Immunol Date: 2011-11-08 Impact factor: 10.793
Authors: Dara G Torgerson; Daniel Capurso; Rasika A Mathias; Penelope E Graves; Ryan D Hernandez; Terri H Beaty; Eugene R Bleecker; Benjamin A Raby; Deborah A Meyers; Kathleen C Barnes; Scott T Weiss; Fernando D Martinez; Dan L Nicolae; Carole Ober Journal: Am J Hum Genet Date: 2012-02-10 Impact factor: 11.025