Genome-wide association study of asthma identifies RAD50-IL13 and HLA-DR/DQ regions.
Genome-wide association study of asthma identifies RAD50-IL13 and HLA-DR/DQ regions.
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DOI：
10.1016/j.jaci.2009.11.018
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发表时间：
2010-02
影响因子：
14.2
通讯作者：
Bleecker, Eugene R.
中科院分区：
文献类型：
--
作者：
Li, Xingnan;Howard, Timothy D.;Zheng, Siqun L.;Haselkorn, Tmirah;Peters, Stephen P.;Meyers, Deborah A.;Bleecker, Eugene R.
哮喘是一种异质性疾病，是由遗传易感性与环境影响的相互作用引起的。全基因组关联研究（GWAS）是研究DNA变异与疾病易感性关联的有力方法。到目前为止，很少有哮喘的GWAS报告。GWAS在严重或难以治疗的哮喘患者中进行，以确定参与哮喘发病机制的基因。在473例TENOR病例和1，892例Illumina普通人群对照中检测了292，443个SNP与哮喘的相关性。在473例TENOR病例和363例无哮喘史的表型对照中，还在确定的候选区域检测了哮喘相关的定量特征（血清总IgE、FEV1、FVC和FEV1/FVC），以进一步分析GWAS结果。在鉴定的候选区域中进行插补，以用于具有更密集SNP覆盖的分析。染色体5q31.1上RAD50-IL13区域的多个SNP与哮喘相关：RAD50内含子2中的rs2244012（P = 3.04E-07）。染色体6p21.3上的HLA-DR/DQ区域也与哮喘相关：HLA-DQB1的3 'UTR中的rs1063355（P = 9.55E-06）。插补在RAD 50的TH2基因座控制区（LCR）3 '中鉴定了几个显著的SNP。插补还确定了HLA-DQB1和HLA-DQA2之间更显著的SNP rs3998159（P = 1.45E-06）。该GWAS证实了TH2细胞因子和抗原呈递基因在全基因组水平上在哮喘中的重要作用，以及对这两个区域进行额外研究以描述其结构复杂性和在哮喘发展中的生物学功能的重要性。
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. GWAS was performed on a population of severe or difficult-to-treat asthmatics to identify genes that are involved in the pathogenesis of asthma. 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. 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. 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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影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
影响因子：
30.8
作者：
Allen, M;Heinzmann, A;Cookson, WOCM
通讯作者：
Cookson, WOCM
影响因子：
5.8
作者：
Johnson, Andrew D.;Handsaker, Robert E.;de Bakker, Paul I. W.
通讯作者：
de Bakker, Paul I. W.
影响因子：
30.8
作者：
Clayton, DG;Walker, NM;Todd, JA
通讯作者：
Todd, JA
影响因子：
56.9
作者：
Gabriel, SB;Schaffner, SF;Altshuler, D
通讯作者：
Altshuler, D