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Böck, A.* ; Urner, K.* ; Eckert, J.K.* ; Salvermoser, M.* ; Laubhahn, K.* ; Kunze, S. ; Kumbrink, J.* ; Hoeppner, M.P.* ; Kalkbrenner, K.* ; Kreimeier, S.* ; Beyer, K.* ; Hamelmann, E.* ; Kabesch, M.* ; Depner, M. ; Hansen, G.* ; Riedler, J.* ; Roponen, M.* ; Schmaußer-Hechfellner, E. ; Barnig, C.* ; Divaret-Chauveau, A.* ; Karvonen, A.M.* ; Pekkanen, J.* ; Frei, R.* ; Roduit, C.* ; Lauener, R.* ; Schaub, B.* ; PASTURE Study Group (Illi, S. ; Pechlivanis, S. ; Pagani, G.)

An integrated molecular risk score early in life for subsequent childhood asthma risk.

Clin. Exp. Allergy 54, 314-328 (2024)
DOI PMC
Creative Commons Lizenzvertrag
Open Access Green as soon as Postprint is submitted to ZB.
BACKGROUND: Numerous children present with early wheeze symptoms, yet solely a subgroup develops childhood asthma. Early identification of children at risk is key for clinical monitoring, timely patient-tailored treatment, and preventing chronic, severe sequelae. For early prediction of childhood asthma, we aimed to define an integrated risk score combining established risk factors with genome-wide molecular markers at birth, complemented by subsequent clinical symptoms/diagnoses (wheezing, atopic dermatitis, food allergy). METHODS: Three longitudinal birth cohorts (PAULINA/PAULCHEN, n = 190 + 93 = 283, PASTURE, n = 1133) were used to predict childhood asthma (age 5-11) including epidemiological characteristics and molecular markers: genotype, DNA methylation and mRNA expression (RNASeq/NanoString). Apparent (ap) and optimism-corrected (oc) performance (AUC/R2) was assessed leveraging evidence from independent studies (Naïve-Bayes approach) combined with high-dimensional logistic regression models (LASSO). RESULTS: Asthma prediction with epidemiological characteristics at birth (maternal asthma, sex, farm environment) yielded an ocAUC = 0.65. Inclusion of molecular markers as predictors resulted in an improvement in apparent prediction performance, however, for optimism-corrected performance only a moderate increase was observed (upto ocAUC = 0.68). The greatest discriminate power was reached by adding the first symptoms/diagnosis (up to ocAUC = 0.76; increase of 0.08, p = .002). Longitudinal analysis of selected mRNA expression in PASTURE (cord blood, 1, 4.5, 6 years) showed that expression at age six had the strongest association with asthma and correlation of genes getting larger over time (r = .59, p < .001, 4.5-6 years). CONCLUSION: Applying epidemiological predictors alone showed moderate predictive abilities. Molecular markers from birth modestly improved prediction. Allergic symptoms/diagnoses enhanced the power of prediction, which is important for clinical practice and for the design of future studies with molecular markers.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Asthma ; Epidemiology ; Genetics ; Paediatrics ; Prevention; Preschool-children; Gene-expression; Dna Methylation; Hay-fever; Prediction; Association; Adolescents; Simulation; Diseases; Models
ISSN (print) / ISBN 0954-7894
e-ISSN 1365-2222
Journal Clinical & Experimental Allergy
Quellenangaben Volume: 54, Issue: 5, Pages: 314-328 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Institute of Asthma and Allergy Prevention (IAP)
Grants Hauner Verein
Kühne foundation
Kuopio Area Respiratory Foundation (AMK)
Yrjö Jahnssonin Säätiö
Finnish Cultural Foundation
Farmers' Social Insurance Institution (Mela)
Reasearch Committee of the Wellbeing Services County of North Savo (Kuopio University Hospital)for the State Research Funding (EVO/VTR)
Juho Vainion Säätiö