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. 2021 May;32(4):709-719.
doi: 10.1111/pai.13438. Epub 2021 Jan 11.

Genetic effects of allergen-specific IgE levels on exhaled nitric oxide in schoolchildren with asthma: The STOPPA twin study

Anna M Hedman  1 , Ralf Kuja-Halkola  1 , Anne K Örtqvist  2   3 , Marianne van Hage  4 , Catarina Almqvist  1   5 , Björn Nordlund  5   6
Affiliations

Genetic effects of allergen-specific IgE levels on exhaled nitric oxide in schoolchildren with asthma: The STOPPA twin study

Anna M Hedman et al. Pediatr Allergy Immunol. 2021 May.

Abstract

Background: Exhaled nitric oxide and blood eosinophils are clinical asthma T-helper type 2 markers in use. Immunoglobulin E (IgE) is often involved in the inflammation associated with atopic asthma. The effect of both blood eosinophils and allergen-specific IgE on exhaled nitric oxide levels is not completely understood. Twin-design studies can improve understanding of the underlying contribution of genetically and/or environmentally driven inflammation markers in asthma. Our aim was to disentangle the covariance between asthma and exhaled nitric oxide into genetic and environmental contributions that can account for inflammation markers in a paediatric population.

Methods: This population-based, cross-sectional twin study enrolled 612 monozygotic (MZ) and same-sex dizygotic (DZ) schoolchildren. Multivariate structural equation modelling was utilized to separate the covariance between asthma and exhaled nitric oxide into genetic and/or environmental effects, taking allergen-specific IgE level and blood eosinophil count into account while controlling for confounding factors.

Results: The cross-twin/cross-trait correlations had a higher magnitude in the MZ twins than in the DZ twins, indicating that genes affect the association. The likelihood ratio test for model fitting resulted in the AE model (ie additive genetic effects, A, and non-shared environmental effects, E) as the most parsimonious. A majority, 73%, of the phenotypic correlation between asthma and exhaled nitric oxide, r = .19 (0.05-0.33), was attributable to genetic effects which mainly was due to the allergen-specific IgE level.

Conclusions: This study indicates that the association between asthma and exhaled nitric oxide in children is to a large extent explained by genetics via allergen-specific IgE level and not blood eosinophils. This might partly explain the clinical heterogeneity in this group. A next step could be to include allergen-specific IgE level in multivariate omic studies.

Keywords: eosinophils; immunoglobulin E; inflammation; twins.

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Conflict of interest statement

The authors report no conflict of interest related to the manuscript content.

Figures

FIGURE 1
FIGURE 1
Cholesky AE model. Path diagram of association within one individual. Capital A and E refer to latent factors, lower‐case a and e refer to path coefficients onto the observed variables. Observed variables are depicted with a square. IgE level = continuous value of allergen‐specific IgE level. Note Variances of latent factors not depicted, but assumed fixed at 1
FIGURE 2
FIGURE 2
Explained phenotypic correlation between asthma and FENO, re‐weighted by sampling probability and adjusted for ICS use. The height of the bar represents the phenotypic correlation, r ph, which is further decomposed into genetic and environmental parts explained by allergen‐specific IgE levels, eosinophils, asthma and FENO. The colour coding represents additive genetic effects, factor A (reddish) or unique environmental effects, factor E (blueish), on the total r ph. IgE level = continuous value of allergen‐specific IgE level
See this image and copyright information in PMC

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