RT Journal文章SR电子T1基因组 - 范围内哮喘加剧虽然吸入皮质类固醇使用JF欧洲呼吸杂志Jo EUR Respir J FD欧洲呼吸学会SP 2003388 Do 10.1183 / 13993003.03388-2020 VO 57是5 A1 Hernandez-Pacheco，Natalia A1 Vijverberg188bet官网地址，Susanne J. A1 Herrera-Luis，Esther A1李，江A1 SiO，杨义A1 Granell，Raquel A1 Rellales，Almudena A1 Maroteau，Cyrielle A1 Lethem，Ryan A1 Perez-Garcia，Javier A1 Farzan，Niloufar A1 Repnik，Katja A1Gorenjak，Mario A1 Soares，Patricia A1 Schieck，Maximilian A1Pérez-Méndez，Lina A1 Berce，Vojko A1 Tavendale，罗杰A1 Eng，Celeste A1 Sardon，Olaia A1 Kull，Oling A1 Mukhopadhyay，Somnath A1 Puremohamed，Munir A1Verhamme, Katia M.C. A1 Burchard, Esteban G. A1 Kabesch, Michael A1 Hawcutt, Daniel B. A1 Melén, Erik A1 Potočnik, Uroš A1 Chew, Fook Tim A1 Tantisira, Kelan G. A1 Turner, Steve A1 Palmer, Colin N. A1 Flores, Carlos A1 Pino-Yanes, Maria A1 Maitland-van der Zee, Anke H. YR 2021 UL //www.qdcxjkg.com/content/57/5/2003388.abstract AB Rationale Substantial variability in response to asthma treatment with inhaled corticosteroids (ICS) has been described among individuals and populations, suggesting the contribution of genetic factors. Nonetheless, only a few genes have been identified to date. We aimed to identify genetic variants associated with asthma exacerbations despite ICS use in European children and young adults and to validate the findings in non-Europeans. Moreover, we explored whether a gene-set enrichment analysis could suggest potential novel asthma therapies.Methods A genome-wide association study (GWAS) of asthma exacerbations was tested in 2681 children of European descent treated with ICS from eight studies. Suggestive association signals were followed up for replication in 538 European asthma patients. 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