@article {Hernandez-Pacheco2003388作者= {Hernandez-Pacheco,纳塔莉亚和Vijverberg Susanne j .和Herrera-Luis以斯帖和李、蒋、Sio杨叶和Granell拉克尔和柯拉勒斯,雅慕黛娜圣母和Maroteau Cyrielle勒瑟姆,瑞恩和Perez-Garcia,哈维尔和大学生,Niloufar Repnik,卡佳Gorenjak,马里奥和苏亚雷斯,帕特里夏·卡里,莱拉和Schieck,马克西米利安和P {\ ' e} rez-M {\ ' e} ndez,莉娜和Berce Vojko Tavendale,罗杰和Eng,天蓝色和Sardon Olaia高尔,荷兰国际集团(ing)和Mukhopadhyay, Somnath Pirmohamed,姆尼尔Verhamme,凯蒂贝拉和今后,埃斯特万·g·Kabesch,迈克尔和Hawcutt丹尼尔·b·和梅尔·{\ ' e n},埃里克和Poto {\ v c}尼克,Uro {\ v s}和咀嚼,福蒂姆和Tantisira,乌克兰g·特纳,史蒂夫·帕尔默,科林·n·弗洛雷斯,卡洛斯和Pino-Yanes,玛丽亚和齐Maitland-van der,安科·h·}={},编辑标题={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},体积= {57}= {5},吸入皮质激素(ICS)治疗哮喘的反应在个体和人群中有很大的差异，这表明遗传因素的作用。188bet官网地址然而，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{\texttimes}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}, issn = {0903-1936}, URL = {//www.qdcxjkg.com/content/57/5/2003388}, eprint = {//www.qdcxjkg.com/content/57/5/2003388.full.pdf}, journal = {European Respiratory Journal} }