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Cited by 31Food Allergy and Anaphylaxis ResearchAsthma and respiratory diseasesDermatology and Skin Diseases

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

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Gabryszewski, Stanislaw J., Chang, Xiao, Dudley, Jesse W., Mentch, Frank, March, Michael, Holmes, John H., Moore, Jason, Grundmeier, Robert W. +2 more·2021·Journal of Allergy and Clinical Immunology
DOI 10.1016/j.jaci.2020.06.026PMC PMC7790850
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Abstract

Background 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. Objective Our aim was to determine the demographic and genetic features that are associated with the major allergic march trajectories. Methods 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. Results 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. Conclusion 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.

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  • In a study carried out in the USA, in 18,596 children with AD, African-American children showed progression from AD to asthma, while those of European-American descent progressed from AD to allergic rhinitis and Asian children progressed from AD to IgE-mediated food allergy.

    “In a study carried out in the USA, in 18,596 children with AD, it was observed that African-American children showed progression from AD to asthma, while those of European-American descent progressed from AD to allergic rhinitis and Asian children progressed from AD to IgE-mediated food allergy.”

    From Update on the pathogenesis of atopic dermatitis. (2024) · cites this paper as [17]

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • AD is usually the first step in the development of the atopic march, as epidermal barrier dysfunction favors the permeation of antigens.

    “AD is usually the first step in the development of the so-called “atopic march”, as the epidermal barrier dysfunction favors the permeation of antigens associated with its onset.”

    From Update on the pathogenesis of atopic dermatitis. (2024) · cites this paper as [17]

    The Introduction states that, based on population-level incidence patterns, the atopic march begins with atopic dermatitis, while noting that individual trajectories can differ. Our copy does not state that epidermal barrier dysfunction permits antigen permeation or identify that mechanism as the reason AD comes first. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • The risk of asthma among children of African-American ancestry was six times higher than among children of European-American ancestry.

    “The risk of asthma among children of African-American ancestry was six times higher than among children of European-American ancestry.”

    From Update on the pathogenesis of atopic dermatitis. (2024) · cites this paper as [17]

    The Results (page not available) associate self-identified Black race with progression from atopic dermatitis to asthma, and the Discussion says asthma disproportionately affects African Americans. The paper does not report a sixfold asthma-risk comparison between children of African-American and European-American ancestry; its finding concerns a specific allergic-disease trajectory and uses self-identified race rather than that ancestry comparison. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The atopic march refers to the sequential progression to allergic rhinitis, food allergy or asthma; however, even such progression has a genetic basis.

    “The atopic march refers to the sequential progression to allergic rhinitis, food allergy or asthma; however, even such progression has a genetic basis.”

    From Update on the pathogenesis of atopic dermatitis. (2024) · cites this paper as [17]

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Cited by

Sorted by citations

Authors
Gabryszewski, S. J., Chang, X., Dudley, J. W., Mentch, F., March, M., Holmes, J. H., Moore, J., Grundmeier, R. W., Hakonarson, H., & Hill, D. A.
Affiliations
  • Children's Hospital of Philadelphia (US)
  • University of Pennsylvania (US)
Corresponding author
Hill, David A.
ORCID
Venue
Journal of Allergy and Clinical Immunology
Publisher
Elsevier BV
Published
2021-02
Volume
147
Issue
2
Pages
677-685.e10
ISSN
0091-6749 (ISSN-L)
DOI
10.1016/j.jaci.2020.06.026
PMC
PMC7790850
OpenAlex
W3041581040
Cited by
31
References
4
Citations by year
2025: 5 · 2024: 7 · 2023: 5 · 2022: 8 · 2021: 4 · 2020: 2
FWCI
3.93
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Allergy and Clinical Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • American Partnership for Eosinophilic Disorders
  • Centre for Applied Genomics
  • National Institutes of Health (AI116794, DK116668, LM010098, LM012601)
  • Children's Hospital of Philadelphia
  • American Academy of Allergy Asthma and Immunology
Topics
  • Health Sciences › Medicine › Immunology and Allergy › Food Allergy and Anaphylaxis Research
  • Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
  • Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
Keywords
allergic march, atopic dermatitis, IgE-mediated food allergy, asthma, allergic rhinitis, racial disparities, ancestry differences, genetic susceptibility loci, disease progression, health disparities
MeSH terms
Adolescent, Child, Child, Preschool, Decision Trees, Female, Humans, Hypersensitivity, Infant, Male, Cluster Analysis, Disease Progression, Racial Groups, Genome-Wide Association Study

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