GWAS鉴定的电子T1 snp通过DNA甲基化和表达影响哮喘风险独联体基因在气道上皮摩根富林明欧洲呼吸杂志乔和J FD欧元欧洲呼吸学会SP 1902079 10.1183/13993003.02079 -2019 A1 Kim 188bet官网地址Soyeon A1《,埃里克A1燕,气A1江,耶鲁A1,荣A1 Boutaoui, Nadia A1 Acosta-Perez,埃德娜A1 Canino, Glorisa A1陈、魏A1青瓷,跨国家哮喘遗传联盟(TAGC)发现了878个与哮喘相关的SNPs。我们假设这些SNPs通过调节气道上皮的基因表达来影响哮喘风险，并进行了表达数量性状位点(eQTL)和中介分析，以确定snp与患有(n=228)和不患有(n=241)哮喘的波多黎各儿童鼻(气道)上皮顺式基因(1mb以内)表达水平之间的直接关联。然后，我们检测了与TAGC SNPs相关的基因在过敏性哮喘中是否存在差异表达(DE)。我们鉴定了418个TAGC SNPs与55个顺式基因表达之间的1150个直接关联。大多数SNPs调节遥远的顺式基因(平均距离约200 kb)。我们的中介分析显示，在5119个(直接和间接)snp基因表达关联中，有4571个(89.2%)是由甲基化介导的。在114个表达与TAGC SNPs相关的基因中，54个在特应性哮喘中是DE，包括新的和以前报道的基因。在72名非裔美国儿童的独立队列中，54个DE基因中有50个可用，21个(42%)在异位性哮喘中也有DE。 Thus, we show that many TAGC SNPs are associated with expression of distant cis-genes in airway epithelium, and that this is predominantly mediated by DNA methylation. Moreover, nearly half of the genes whose expression in airway epithelium is associated with TAGC SNPs are also DE in atopic asthma. Our findings support a key role of regulation of airway epithelial gene expression on atopic asthma in children.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: S. Kim has nothing to disclose.Conflict of interest: E. Forno has nothing to disclose.Conflict of interest: Q. Yan has nothing to disclose.Conflict of interest: Y. Jiang has nothing to disclose.Conflict of interest: R. Zhang has nothing to disclose.Conflict of interest: N. Boutaoui has nothing to disclose.Conflict of interest: E. Acosta-Pérez has nothing to disclose.Conflict of interest: G. Canino has nothing to disclose.Conflict of interest: W. Chen has nothing to disclose.Conflict of interest: J.C. Celedón has received research materials from GSK and Merck (inhaled steroids) and Pharmavite (vitamin D and Placebo capsules), in order to provide medications free of cost to participants in NIH-funded studies, unrelated to the current work.