Gene-environment interactions in childhood asthma revisited; expanding the interaction concept

Abstract

Investigation of gene-environment interactions (GxE) may provide important insights into the gene regulatory framework in response to environmental factors of relevance for childhood asthma. Over the years, different methodological strategies have been applied, more recently using genome-wide approaches. The best example to date is the major asthma locus on the 17q12-21 chromosome region, viral infections, and airway epithelium processes where recent studies have shed much light on mechanisms in childhood asthma. However, there are challenges with the traditional single variant-single exposure interaction models, as they do not encompass the complexity and cumulative effects of multiple exposures or multiple genetic variants. As such, we need to redefine our traditional GxE thinking, and we propose in this review to expand the GxE concept by also evaluating other omics layers, such as epigenetics, transcriptomics, metabolomics, and proteomics. In addition, host factors such as age, gender, and other exposures are very likely to influence GxE effects and need firmly to be considered in future studies.

Keywords: asthma; children; environmental exposure; epigenetics; genetics; genome-wide interaction study; methylation; omics.

FIGURE 1

Overview of the environmental and host factors in interaction with the genetic variation affecting childhood asthma. Outdoor exposures are shown on the left‐hand side, including farming environment, outdoor allergens, and ambient air pollution. Indoor factors are illustrated on the right: for example, tobacco smoke, cooking and heating, allergens from furred pets, house dust mites, and molds. Host factors are presented on top comprising age (not shown), gender, SES, psychosocial and perinatal factors, and diet and respiratory infections in early life. These interact with the individual's genetic composition and epigenetic modifications altering the risk of asthma‐related traits