TY -的T1 - snp被GWAS影响眼疲劳ma risk through DNA methylation and expression of cis-genes in airway epithelium JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.02079-2019 SP - 1902079 AU - Kim, Soyeon AU - Forno, Erick AU - Yan, Qi AU - Jiang, Yale AU - Zhang, Rong AU - Boutaoui, Nadia AU - Acosta-Pérez, Edna AU - Canino, Glorisa AU - Chen, Wei AU - Celedón, Juan C. Y1 - 2019/01/01 UR - //www.qdcxjkg.com/content/early/2019/11/26/13993003.02079-2019.abstract N2 - The Trans-National Asthma Genetic Consortium (TAGC) identified 878 SNPs associated with asthma. We hypothesised that those SNPs affect asthma risk by regulating gene expression in airway epithelium, and conducted expression quantitative trait loci (eQTL) and mediation analyses to identify direct associations between the SNPs and expression levels of cis-genes (within 1 Mb) in nasal (airway) epithelium from Puerto Rican children with (n=228) and without (n=241) asthma. We then tested whether genes whose expression is associated with TAGC SNPs are differentially expressed (DE) in atopic asthma. We identified 1150 direct associations between 418 TAGC SNPs and the expression of 55 cis-genes. Most SNPs regulate distant cis-genes (average distance ∼200 kb). Our mediation analysis showed that 4571 (89.2%) of 5119 (direct and indirect) SNP-gene expression associations are mediated by methylation. Of 114 genes whose expression is associated with TAGC SNPs, 54 are DE in atopic asthma, including novel and previously reported genes. In an independent cohort of 72 African American children, 50 of the 54 DE genes were available, and 21 (42%) were also DE in atopic asthma. 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. ER -