Genome‐wide association studies of exacerbations in children using long‐acting beta2‐agonists. Issue 6 (29th March 2021)

• Record Type: Journal Article
• Authors: Slob, Elise M. A.; Richards, Levi B.; Vijverberg, Susanne J. H.; Longo, Cristina; Koppelman, Gerard H.; Pijnenburg, Mariëlle W. H.; Bel, Elisabeth H. D.; Neerincx, Anne H.; Herrera Luis, Esther; Perez‐Garcia, Javier; Tim Chew, Fook; Yie Sio, Yang; Andiappan, Anand K.; Turner, Steve W.; Mukhopadhyay, Somnath; Palmer, Colin N. A.; Hawcutt, Daniel; Jorgensen, Andrea L.; Burchard, Esteban G.; Hernandez‐Pacheco, Natalia; Pino‐Yanes, Maria; Maitland‐van der Zee, Anke H.
• Editors: Kalaycı, Ömer
• Is Part Of: Pediatric allergy and immunology. Volume 32:Issue 6(2021)
• Page Start: 1197
• Page End: 1207
• Publication Date: 2021-03-29
• Subjects: childhood asthma -- exacerbations -- genetic polymorphism -- long‐acting beta2‐agonist -- pharmacogenetics; Allergy in children -- Periodicals; Immunologic diseases in children -- Periodicals; 617
• DOI: 10.1111/pai.13494
• Languages: English
• ISSNs: 0905-6157

Abstract

Abstract: 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. Abstract :