Berce, V

Burchard, E

Consortia, PiCA SysPharmPedia

Farzan, N

Flores, C

Francis, B

Hawcutt, D

Hernandez-Pacheco, N

Kabesch, M

Maitland-van der Zee, A

Palmer, C

Pino-Yanes, M

Pirmohamed, M

Potocnik, U

Repnik, K

Schieck, M

Vijverberg, S

University of Liverpool Repository

Genome-wide association study of inhaled corticosteroid response in African-admixed children with asthmaNatalia Hernandez-Pacheco,1 Niloufar Farzan,2,3 Susanne J Vijverberg,2,3 Ben Francis,4 Maximilian Schieck,5,6 Munir Pirmohamed,7 Daniel B Hawcutt,4,8 Michael Kabesch,5,6 Colin Palmer,9 Carlos Flores,1,10 Anke H Maitland-van der Zee,2,3 Esteban G Burchard,*11,12 Maria Pino-Yanes*1,10 on behalf of the PiCA and SysPharmPedia consortia1Research Unit, Hospital Universitario N.S. de Candelaria, Universidad de La Laguna, Santa Cruz de Tenerife, Spain.2Division of Pharmacoepidemiology and Clinical Pharmacology, Faculty of Science, Utrecht University, Utrecht, Netherlands.3Department of Respiratory Medicine, Academic Medical Center (AMC). University of Amsterdam, Amsterdam, the Netherlands.4Department of Women's and Children's Health, University of Liverpool, Liverpool, UK.5Dept. of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO), Regensburg, Germany.6Dept. of Pediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany. Member of the German Lung Research Center (DZL).7Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.8Alder Hey Children's Hospital, Liverpool, UK.9Population Pharmacogenetics Group, Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom10CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.11Department of Medicine, University of California, San Francisco, CA, United States.12Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, United States.* These authors contributed equally to this workIntroduction: Inhaled corticosteroids (ICS) are the most widely prescribed and effective medication to control asthma symptoms. However, this treatment is insufficient to avoid severe exacerbations in many patients, particularly in African Americans. A few genome-wide association studies (GWAS) of ICS have been performed, but none of them in African-admixed populations. Here, we aimed to identify loci associated with asthma exacerbations in children taking ICS.Methods: Within the PiCA consortium, a meta-analysis of two GWAS of asthma exacerbations was performed in 1,401 African-admixed children from the GALA II and SAGE II studies. Imputation of genetic variants was carried out using the Haplotype Reference Consortium as reference panel and association testing was performed by means of logistic regression models. A total of 8.6 million genetic variants with minor allele frequency ≥1% were meta-analyzed. Variants with p≤5x10-6 were followed up for replication in 1,204 European asthmatic patients from three different studies (PACMAN, followMAGICS, and PASS).Results: A total of 27 polymorphisms were suggestively associated with asthma exacerbations (p≤5x10-6) in African-admixed populations and 3 of them showed evidence of replication in European individuals (p≤5.4x10-3). These were located in the intergenic region of the APOBEC3B and APOBEC3C genes, which have been linked with viral infections.Conclusions: This study revealed the association of a novel locus with asthma exacerbations in children despite the use of ICS.This work was supported by Instituto de Salud Carlos III (AC15/00015) within the ERACoSysMed 1st Joint Transnational Call (SysPharmPedia) from the European Union, under the Horizon 2020.

Identification of a novel locus associated with asthma treatment response with inhaled corticosteroids in African-admixed children

http://livrepository.liverpool.ac.uk/3064962/1/Abstract_NHP_ERS2017_African%20AHM_CF_EGB.doc

Identification of a novel locus associated with asthma treatment response with inhaled corticosteroids in African-admixed children

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