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

Böck, Andreas ; Urner, Kathrin; Eckert, Jana Kristin ; Salvermoser, Michael ; Laubhahn, Kristina ; Kunze, Sonja ; Kumbrink, Jörg; Hoeppner, Marc P. ; Kalkbrenner, Kathrin; Kreimeier, Simone ; Beyer, Kirsten ; Hamelmann, Eckard ; Kabesch, Michael ; Depner, Martin; Hansen, Gesine ; Riedler, Josef; Roponen, Marjut ; Schmausser‐Hechfellner, Elisabeth ; Barnig, Cindy ; Divaret‐Chauveau, Amandine ; Karvonen, Anne M. ; Pekkanen, Juha ; Frei, Remo; Roduit, Caroline ; Lauener, Roger und Schaub, Bianca (2024): An integrated molecular risk score early in life for subsequent childhood asthma risk. In: Clinical & Experimental Allergy, Bd. 54, Nr. 5: S. 314-328

Abstract

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Klinikum der LMU München > Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0954-7894
• Sprache: Englisch