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Genomics and Pharmacogenomics of Severe Childhood Asthma

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Severe Asthma in Children and Adolescents

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Abstract

Twin studies have shown that asthma has a heritability of more than 50%, indicating that genetic factors play a major role in its pathogenesis and are an important key to understanding the underlying disease mechanisms. Heritability is higher for childhood compared to adult asthma, and genetics also seem to be partly responsible for determining symptom severity, suggesting that genetic studies might be particularly relevant in relation to severe childhood asthma. Furthermore, the poor response to standard treatments in severe asthma indicates that this phenotype might be associated with distinct underlying mechanisms, potentially driven by genetics, separating it from milder disease. In addition to studying the genetic code (or genome), the study of genomics includes methodological approaches such as epigenetics (of importance for gene regulation) and transcriptomics (studies of gene expression). All of these are “mechanistic tools” with the potential to increase understanding of basic disease processes and provide the basis for improved treatment. In this chapter we will focus on (1) genomic approaches contributing to our understanding of disease mechanisms and (2) genomic approaches used to predict and understand differences in treatment response between individuals, also termed pharmacogenomics. Since relatively few genomic studies have focused specifically on the phenotype of severe childhood asthma, we will also discuss the implications of results from studies on milder disease and studies of severe asthma in adults.

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Authors and Affiliations

  1. Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Gentofte, Northern Sealand, Denmark

    Klaus Bønnelykke

  2. Department of Pediatric Pulmonology and Allergology, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Gerard H. Koppelman

  3. GRIAC Research Institute, Groningen, The Netherlands

    Gerard H. Koppelman

  4. Department of Respiratory Medicine, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands

    Elise M. A. Slob, Susanne J. H. Vijverberg & Anke H. Maitland-van der Zee

  5. Department of Paediatric Pulmonology, Emma Children’s Hospital, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands

    Elise M. A. Slob, Susanne J. H. Vijverberg & Anke H. Maitland-van der Zee

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  1. Klaus Bønnelykke
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Correspondence to Klaus Bønnelykke .

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  1. Children’s Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA

    Erick Forno

  2. Imperial College London, National Heart & Lung Institute, London, UK

    Sejal Saglani

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Bønnelykke, K., Koppelman, G.H., Slob, E.M.A., Vijverberg, S.J.H., Maitland-van der Zee, A.H. (2020). Genomics and Pharmacogenomics of Severe Childhood Asthma. In: Forno, E., Saglani, S. (eds) Severe Asthma in Children and Adolescents. Springer, Cham. https://doi.org/10.1007/978-3-030-27431-3_15

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