% 0期刊文章% Hernandez-Pacheco,纳塔莉亚% Vijverberg, Susanne Herrera-Luis j . %,以斯帖%李,江% Sio,杨叶% Granell,拉奎尔%柯拉勒斯,雅慕黛娜圣母% Maroteau, Cyrielle %勒瑟姆,瑞安% Perez-Garcia,哈维尔·%的大学生,Niloufar % Repnik,卡佳% Gorenjak,马里奥%苏亚雷斯,帕特里夏·%卡里,莱拉Schieck %,马克西米利安% Perez-Mendez,莉娜% Berce, Vojko % Tavendale,罗杰% Eng, Celeste % Sardon, Olaia %高尔,荷兰国际集团(ing) % Mukhopadhyay, Somnath % Pirmohamed,姆尼尔% Verhamme,凯蒂m %今后,埃斯特万·g·% Kabesch,迈克尔% Hawcutt,丹尼尔·b·% Melen, Erik %一个Potoč尼克,Uroš%咀嚼,福蒂姆% Tantisira,乌克兰特纳g . %,Steve A Palmer, Colin N. A Flores, Carlos A Pino-Yanes, Maria A Maitland-van der Zee，Anke h . % % T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% D J 2021% R 10.1183/13993003.03388 -2020%欧洲呼吸杂志X % P 2003388 % V 57% N 5%理由大幅变化对哮喘治疗的反应与吸入激素(ICS)个人和中被描述这表明遗传因素的作用。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。 Further evaluation was performed in 1773 non-Europeans. 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 %U //www.qdcxjkg.com/content/erj/57/5/2003388.full.pdf