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Genetic effects of inflammation markers on exhaled nitric oxide in schoolchildren with asthma: A twin study
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  • Anna Hedman,
  • Ralf Kuja-Halkola,
  • Anne Örtqvist,
  • Marianne van Hage,
  • Catarina Almqvist,
  • Björn Nordlund
Anna Hedman
Karolinska Institute
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Ralf Kuja-Halkola
Karolinska Institute
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Anne Örtqvist
Karolinska Institutet
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Marianne van Hage
Karolinska Institute
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Catarina Almqvist
Karolinska Institutet
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Björn Nordlund
Karolinska Institutet
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Background: Exhaled nitric oxide and blood eosinophils are clinical asthma 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 as the most parsimonious. A majority, 73%, of the phenotypic correlation between asthma and exhaled nitric oxide, r=0.19 (0.05–0.33), was attributable to genetic effects which mainly was due to the allergen-specific IgE level. Conclusions: This study indicate that the association between asthma - exhaled nitric oxide in children is to a large extent explained by genetics via allergen-specific IgE-level but 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.

Peer review status:ACCEPTED

02 Jun 2020Submitted to Pediatric Allergy and Immunology
08 Jun 2020Reviewer(s) Assigned
23 Jun 2020Review(s) Completed, Editorial Evaluation Pending
25 Jun 2020Editorial Decision: Revise Major
28 Sep 20201st Revision Received
29 Sep 2020Review(s) Completed, Editorial Evaluation Pending
29 Sep 2020Reviewer(s) Assigned
06 Nov 2020Editorial Decision: Revise Major
07 Dec 20202nd Revision Received
09 Dec 2020Review(s) Completed, Editorial Evaluation Pending
16 Dec 2020Editorial Decision: Accept