Unsupervised modeling and genome-wide association identify novel features of allergic march trajectories

• Published in: Journal of allergy and clinical immunology 2021-02, Vol.147 (2), p.677-685.e10
• Main Authors: Gabryszewski, Stanislaw J., Chang, Xiao, Dudley, Jesse W., Mentch, Frank, March, Michael, Holmes, John H., Moore, Jason, Grundmeier, Robert W., Hakonarson, Hakon, Hill, David A.
• Format: Article
• Language: English
• Subjects: Adolescent; allergic march; allergic rhinitis; allergic trajectory; asthma; atopic dermatitis; Atopic march; Child; Child, Preschool; Cluster Analysis; Decision Trees; Disease Progression; epidemiology; Female; Genome-Wide Association Study; Humans; Hypersensitivity - ethnology; Hypersensitivity - genetics; IgE-mediated food allergy; Infant; Male; Racial Groups
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2020.06.026

The allergic march refers to the natural history of allergic conditions during infancy and childhood. However, population-level disease incidence patterns do not necessarily reflect the development of allergic disease in individuals. A better understanding of the factors that predispose to different allergic trajectories is needed. Our aim was to determine the demographic and genetic features that are associated with the major allergic march trajectories. Presence or absence of common allergic conditions (atopic dermatitis [AD], IgE-mediated food allergy [IgE-FA], asthma, and allergic rhinitis [AR]) was ascertained in a pediatric primary care birth cohort of 158,510 subjects. Hierarchic clustering and decision tree modeling were used to associate demographic features with allergic outcomes. Genome-wide association study was used to test for risk loci associated with specific allergic trajectories. We found an association between self-identified black race and progression from AD to asthma. Conversely, Asian or Pacific Islander race was associated with progression from AD to IgE-mediated food allergy, and white race was associated with progression from AD to AR. Genome-wide association study of trajectory groups identified risk loci associated with progression from AD to asthma (rs60242841) and from AD to AR (rs9565267, rs151041509, and rs78171803). Consistent with our epidemiologic associations, rs60242841 was more common in individuals of African ancestry than in individuals of European ancestry, whereas rs9565267 and rs151041509 were more common in individuals of European ancestry than in individuals of African ancestry. We have identified novel associations between race and progression along distinct allergic trajectories. Ancestral genetic differences may contribute to these associations. These results uncover important health disparities, refine the concept of the allergic march, and represent a step toward developing individualized medical approaches for these conditions. [Display omitted]