TY - JOUR T1 - Genome-wide association study of asthma exacerbations in European children treated with inhaled corticosteroids JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/1393003.congress-2017.PA1817 VL - 50 IS - suppl 61 SP - PA1817 AU - Susanne J. H. Vijverberg AU - Natalia Hernandez-Pacheco AU - Niloufar Farzan AU - Ben Francis AU - Carlos Flores AU - Maximilian Schieck AU - Patricia Soares AU - Leila Karimi AU - Roger Tavendale AU - Vojko Berce AU - Katja Repnik AU - Katia Verhamme AU - Uroš PotočNik AU - Somnath Mukhopadhyay AU - Munir Pirmohamed AU - Colin Palmer AU - Steve Turner AU - Daniel Hawcutt AU - Michael Kabesch AU - Maria Pino-Yanes AU - Anke-Hilse Maitland-Van Der Zee Y1 - 2017/09/01 UR - http://erj.ersjournals.com/content/50/suppl_61/PA1817.abstract N2 - Introduction: Inhaled corticosteroids (ICS) are the most common asthma controller medication. However, a high proportion of patients does not respond to this medication and suffer exacerbations. We performed a genome-wide association study (GWAS) to identify genes associated with asthma exacerbations in European children taking ICS.Methods: Within the PiCA consortium, we performed a GWAS meta-analysis of asthma exacerbations across three European cohorts (PACMAN, PASS, and followMAGICS) including 1,204 asthmatic children treated with ICS. Imputation of genetic variants was performed using the Haplotype Reference Consortium as reference panel by means of the Michigan Imputation Server. Association testing of 7.5 million genetic variants with minor allele frequency ≥1% was performed using logistic regression models and results were meta-analyzed.Results: A total of 74 variants were suggestively associated with asthma exacerbations despite the use of ICS (p≤5x10-6). The most significant variants were located in 9 different loci (minimum p-value=2.3x10-7), including one gene previously identified as associated with ICS response in Asian populations (ALLC). Additionally, novel associations were revealed in biologically plausible genes with drug metabolism functions and in genes belonging to the Wnt/β-catenin signaling pathway.Conclusions: We identified several novel genes suggestively associated with asthma exacerbations despite the use of ICS. Validation will be performed in further independent studies.Study supported by Instituto de Salud Carlos III (AC15/00015) and ERACoSysMed 1st Joint Transnational Call (SysPharmPedia). # shared first and last authors ER -