Epigenomics and Transcriptomics in the Prediction and Diagnosis of Childhood Asthma: Are We There Yet?

Abstract

Asthma is the most common non-communicable chronic disease of childhood. Despite its high prevalence, to date we lack methods that are both efficient and accurate in diagnosing asthma. Most traditional approaches have been based on garnering clinical evidence, such as risk factors and exposures. Given the high heritability of asthma, more recent approaches have looked at genetic polymorphisms as potential "risk factors." However, genetic variants explain only a small proportion of asthma risk, and have been less than optimal at predicting risk for individual subjects. Epigenomic studies offer significant advantages over previous approaches. Epigenetic regulation is highly tissue-specific, and can induce both short- and long-term changes in gene expression. Such changes can start in utero, can vary throughout the life span, and in some instances can be passed on from one generation to another. Most importantly, the epigenome can be modified by environmental factors and exposures, and thus epigenetic and transcriptomic profiling may yield the most accurate risk estimates for a given patient by incorporating environmental (and treatment) effects throughout the lifespan. Here we will review the most recent advances in the use of epigenetic and transcriptomic analysis for the early diagnosis of asthma and atopy, as well as challenges and future directions in the field as it moves forward. We will particularly focus on DNA methylation, the most studied mechanism of epigenetic regulation.

Keywords: DNA methylation; RNA sequencing; childhood asthma; epigenetics; transcriptomics.

Figure 1

Overview of mechanisms involved in epigenetic regulation of gene expression. There are several epigenetic mechanisms that regulate gene expression during development and in response to environmental and other factors. DNA methylation suppresses (down-regulates) gene expression. Histone modification can occur via different pathways that lead to different effects (e.g., histone acetylation facilitates gene expression). A third group of mechanisms, post-translational RNA modification, is not pictured here for clarity. Modified from the U.S. National Institutes of Health (https://commonfund.nih.gov/epigenomics/figure).

Figure 2

Pathway analysis of nasal epithelium epigenomics and atopy. Overlapping canonical pathways enriched in the analysis of DNA methylation and gene expression in nasal epithelium and childhood atopy. Reproduced with permission from Forno et al. (33), ©The Lancet Respiratory Medicine 2018 (https://doi.org/10.1016/S2213-2600(18)30466-1).