TY - T1的全基因组关联研究哮喘急性加重尽管吸入皮质类固醇使用摩根富林明-欧洲呼吸杂志》乔和J - 10.1183/13993003.03388 -2020欧元六世- 57 - 5 SP - 2003388 AU Hernandez-Pacheco娜塔莉亚盟——Vijverberg Susanne J . AU - Herrera-Luis以斯帖非盟-李,蒋盟——Sio杨叶盟——Granell拉奎尔AU -柯拉勒斯,雅慕黛娜圣母盟——Maroteau Cyrielle AU -勒瑟姆,瑞安非盟- Perez-Garcia哈维尔盟——大学生,Niloufar盟——Repnik Katja盟——Gorenjak马里奥AU -苏亚雷斯,帕特丽夏盟——卡里,莱拉AU - Schieck,马克西米利安非盟- Perez-Mendez莉娜盟——Berce Vojko AU - Tavendale,罗杰·AU - Eng Celeste盟——SardonOlaia AU -库尔,荷兰国际集团(ing)盟——Mukhopadhyay, Somnath盟——Pirmohamed姆尼尔盟——Verhamme凯蒂贝拉盟——今后Esteban g . AU - Kabesch迈克尔AU - Hawcutt,丹尼尔•b . AU - Melen Erik AU - Potoč尼克,Uroš盟——咀嚼,蒂姆福盟——Tantisira乌克兰g . AU -特纳,史蒂夫AU -帕尔默,科林·n . AU -弗洛雷斯,卡洛斯AU - Pino-Yanes,玛丽亚盟——Maitland-van der Zee安科·h·A2 - Y1 - 2021/05/01 UR - //www.qdcxjkg.com/content/57/5/2003388.abstract N2 -理由大幅变化对哮喘治疗的反应与吸入激素(ICS)被描述个体和人群,表明遗传因素的贡献。然而，迄今为止，只有少数几个基因被识别出来。我们的目的是识别与哮喘加重相关的遗传变异，尽管ICS在欧洲儿童和年轻人中使用，并验证非欧洲人的研究结果。此外，我们还探索了基因集富集分析是否可以提供潜在的新型哮喘治疗方法。方法对来自8项研究的2681名接受ICS治疗的欧洲后裔儿童进行哮喘加重的全基因组关联研究(GWAS)。对538名欧洲哮喘患者的复制情况进行了提示性相关信号的随访。1773年对非欧洲人进行了进一步的评估。 Variants revealed by published GWAS were assessed for replication. Additionally, gene-set enrichment analysis focused on drugs was performed.Results 10 independent variants were associated with asthma exacerbations despite ICS treatment in the discovery phase (p≤5×10−6). Of those, one variant at the CACNA2D3-WNT5A locus was nominally replicated in Europeans (rs67026078; p=0.010), but this was not validated in non-European populations. Five other genes associated with ICS response in previous studies were replicated. Additionally, an enrichment of associations in genes regulated by trichostatin A treatment was found.Conclusions The intergenic region of CACNA2D3 and WNT5A was revealed as a novel locus for asthma exacerbations despite ICS treatment in European populations. Genes associated were related to trichostatin A, suggesting that this drug could regulate the molecular mechanisms involved in treatment response.A genome-wide association study of asthma exacerbations despite inhaled corticosteroid treatment in childhood asthma revealed a novel association at the CACNA2D3-WNT5A locus and suggested trichostatin A as a potential asthma therapy https://bit.ly/3nxWLPD ER -