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Asthma Exacerbations: The Genes Behind the Scenes

Herrera-Luis E1, Forno E2, Celedón JC2, Pino-Yanes M1,3,4

1Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna (ULL), La Laguna, Tenerife, Spain
2Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, University  of Pittsburgh, Pittsburgh, Pennsylvania, USA
3CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain
4Instituto de Tecnologías Biomédicas (ITB), Universidad de La Laguna (ULL), La Laguna, Tenerife, Spain

J Investig Allergol Clin Immunol 2023; Vol 33(2) : 76-94
doi: 10.18176/jiaci.0878

The clinical and socioeconomic burden of asthma exacerbations (AEs) constitutes a major public health problem. In the last 4 years, there has been an increase in ethnic diversity in candidate-gene and genome-wide association studies of AEs, which in the latter case led to the identification of novel genes and underlying pathobiological processes. Pharmacogenomics, admixture mapping analyses, and the combination of multiple “omics” layers have helped to prioritize genomic regions of interest and/or facilitated our understanding of the functional consequences of genetic variation. Nevertheless, the field still lags behind the genomics of asthma, where a vast compendium of genetic approaches has been used (eg, gene–environment interactions, next-generation sequencing, and polygenic risk scores). Furthermore, the roles of the DNA methylome and histone modifications in AEs have received little attention, and microRNA findings remain to be validated in independent studies. Likewise, the most recent transcriptomic studies highlight the importance of the host–airway microbiome interaction in the modulation of risk of AEs. Leveraging -omics and deep-phenotyping data from subtypes or homogenous subgroups of patients will be crucial if we are to overcome the inherent heterogeneity of AEs, boost the identification of potential therapeutic targets, and implement precision medicine approaches to AEs in clinical practice.

Key words: Asthma exacerbations, Genomics, Epigenetics, Transcriptomics