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In Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology

BACKGROUND : The asthma syndrome is influenced by hereditary and environmental factors. With the example of farm exposure, we study whether genetic and environmental factors interact for asthma.

METHODS : Statistical learning approaches based on penalized regression and decision trees were used to predict asthma in the GABRIELA study with 850 cases (9% farm children) and 857 controls (14% farm children). Single-nucleotide polymorphisms (SNPs) were selected from a genome-wide dataset based on a literature search or by statistical selection techniques. Prediction was assessed by receiver operating characteristics (ROC) curves and validated in the PASTURE cohort.

RESULTS : Prediction by family history of asthma and atopy yielded an area under the ROC curve (AUC) of 0.62 [0.57-0.66] in the random forest machine learning approach. By adding information on demographics (sex and age) and 26 environmental exposure variables, the quality of prediction significantly improved (AUC=0.65 [0.61-0.70]). In farm children, however, environmental variables did not improve prediction quality. Rather SNPs related to IL33 and RAD50 contributed significantly to the prediction of asthma (AUC=0.70 [0.62-0.78]).

CONCLUSIONS : Asthma in farm children is more likely predicted by other factors as compared to non-farm children though in both forms, family history may integrate environmental exposure, genotype, and degree of penetrance.

Krautenbacher Norbert, Kabesch Michael, Horak Elisabeth, Braun-Fahrländer Charlotte, Genuneit Jon, Boznanski Andrzej, von Mutius Erika, Theis Fabian, Fuchs Christiane, Ege Markus J

2020-Sep-30

Childhood asthma, GWAS, SNPs, environment, farming, machine learning, penalized regression, random forest, risk prediction, statistical learning