Genome-wide association studies of exacerbations in children using long-acting beta2-agonists.

Autor: Slob EMA; Department of Respiratory Disease, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.; Pediatric Respiratory Medicine, Emma Children's Hospital, Amsterdam UMC, Amsterdam, The Netherlands., Richards LB; Department of Respiratory Disease, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands., Vijverberg SJH; Department of Respiratory Disease, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.; Pediatric Respiratory Medicine, Emma Children's Hospital, Amsterdam UMC, Amsterdam, The Netherlands.; Division of Pharmacoepidemiology and Clinical Pharmacology, Faculty of Science, Utrecht University, Utrecht, Netherlands., Longo C; Department of Respiratory Disease, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands., Koppelman GH; Department of Paediatric, Pulmonology & Paediatric Allergology, University Medical Center Groningen, Beatrix Children's Hospital, University of Groningen, Groningen, The Netherlands.; University Medical Center Groningen, Groningen Research Institute for Asthma & COPD (GRIAC), University of Groningen, Groningen, The Netherlands., Pijnenburg MWH; Division of Respiratory Medicine and Allergology, Department of Paediatrics, Erasmus MC - Sophia, University Medical Center Rotterdam, Rotterdam, The Netherlands., Bel EHD; Department of Respiratory Disease, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands., Neerincx AH; Department of Respiratory Disease, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands., Herrera Luis E; Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, Santa Cruz de Tenerife, Spain., Perez-Garcia J; Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, Santa Cruz de Tenerife, Spain., Tim Chew F; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Yie Sio Y; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Andiappan AK; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.; Department of Biological Sciences, National University of Singapore, Singapore, Singapore., Turner SW; Department of Child Health, University of Aberdeen, Aberdeen, UK., Mukhopadhyay S; Academic Department of Paediatrics, Royal Alexandra Children's Hospital, Brighton and Sussex Medical School, Brighton, UK.; Population Pharmacogenetics Group, Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK., Palmer CNA; Population Pharmacogenetics Group, Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK., Hawcutt D; Department of Women's and Children's Health, University of Liverpool, Liverpool, UK.; NIHR Alder Hey Clinical Research Facility, Alder Hey Children's Hospital, Liverpool, UK., Jorgensen AL; Department of Health Data Science, University of Liverpool, Liverpool, UK., Burchard EG; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA., Hernandez-Pacheco N; Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, Santa Cruz de Tenerife, Spain., Pino-Yanes M; Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, Santa Cruz de Tenerife, Spain.; Research Unit, Hospital Universitario N.S. de Candelaria, Universidad de La Laguna, Santa Cruz de Tenerife, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.; Instituto de Tecnologías Biomédicas (ITB), Universidad de La Laguna, Santa Cruz de Tenerife, Spain., Maitland-van der Zee AH; Department of Respiratory Disease, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.; Pediatric Respiratory Medicine, Emma Children's Hospital, Amsterdam UMC, Amsterdam, The Netherlands.; Division of Pharmacoepidemiology and Clinical Pharmacology, Faculty of Science, Utrecht University, Utrecht, Netherlands.
Jazyk: angličtina
Zdroj: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology [Pediatr Allergy Immunol] 2021 Aug; Vol. 32 (6), pp. 1197-1207. Date of Electronic Publication: 2021 Mar 29.
DOI: 10.1111/pai.13494
Abstrakt: Background: Some children with asthma experience exacerbations despite long-acting beta2-agonist (LABA) treatment. While this variability is partly caused by genetic variation, no genome-wide study until now has investigated which genetic factors associated with risk of exacerbations despite LABA use in children with asthma. We aimed to assess whether genetic variation was associated with exacerbations in children treated with LABA from a global consortium.
Methods: A meta-analysis of genome-wide association studies (meta-GWAS) was performed in 1,425 children and young adults with asthma (age 6-21 years) with reported regular use of LABA from six studies within the PiCA consortium using a random effects model. The primary outcome of each study was defined as any exacerbation within the past 6 or 12 months, including at least one of the following: 1) hospital admissions for asthma, 2) a course of oral corticosteroids or 3) emergency room visits because of asthma.
Results: Genome-wide association results for a total of 82 996 common single nucleotide polymorphisms (SNPs, MAF ≥1%) with high imputation quality were meta-analysed. Eight independent variants were suggestively (P-value threshold ≤5 × 10 -6 ) associated with exacerbations despite LABA use.
Conclusion: No strong effects of single nucleotide polymorphisms (SNPs) on exacerbations during LABA use were identified. We identified two loci (TBX3 and EPHA7) that were previously implicated in the response to short-acting beta2-agonists (SABA). These loci merit further investigation in response to LABA and SABA use.
(© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)
Databáze: MEDLINE
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