Abbonarsi

Unsupervised modeling and genome-wide association identify novel features of allergic march trajectories - 04/02/21

Doi : 10.1016/j.jaci.2020.06.026 
Stanislaw J. Gabryszewski, MD, PhD a, , Xiao Chang, PhD b, , Jesse W. Dudley, MS c, Frank Mentch, PhD b, Michael March, PhD b, John H. Holmes, PhD d, Jason Moore, PhD d, Robert W. Grundmeier, MD c, e, Hakon Hakonarson, MD, PhD b, e, f, David A. Hill, MD, PhD a, e, g,
a Division of Allergy and Immunology, Children’s Hospital of Philadelphia, Philadelphia, Pa 
b Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, Pa 
c Department of Biomedical and Health Informatics, Children’s Hospital of Philadelphia, Philadelphia, Pa 
d Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa 
e Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa 
f Division of Pulmonary Medicine, Children’s Hospital of Philadelphia, Philadelphia, Pa 
g Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa 

Corresponding author: David A. Hill, MD, PhD, Division of Allergy and Immunology, Children’s Hospital of Philadelphia, Abramson Research Building, 1208B, 3615 Civic Center Blvd, Philadelphia, PA 19104.Division of Allergy and ImmunologyChildren’s Hospital of PhiladelphiaAbramson Research Building1208B3615 Civic Center BlvdPhiladelphiaPA19104

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.

Il testo completo di questo articolo è disponibile in PDF.

Graphical abstract




Il testo completo di questo articolo è disponibile in PDF.

Key words : Atopic march, allergic march, allergic trajectory, atopic dermatitis, IgE-mediated food allergy, asthma, allergic rhinitis, epidemiology, genome-wide association study

Abbreviations used : AD, AR, CHOP, GWAS, ICD, IgE-FA, MAF, SNP, TOPMed, UKB


Mappa


 Supported by the National Institutes of Health (grants DK116668 [to D.A.H.], LM010098 [to J.M.], AI116794 [to J.M.], and LM012601 [to J.M.]); the Children’s Hospital of Philadelphia Endowed Chair in Genomic Research (to H.H.); the American College of Allergy, Asthma, and Immunology (to D.A.H.); the American Academy of Allergy, Asthma, and Immunology (to D.A.H.); the American Partnership for Eosinophilic Disorders (to D.A.H.); and the Children’s Hospital of Philadelphia Research Institute Developmental awards to the Hill Lab and the Center for Applied Genomics (to H.H.). The content of this work is the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
 Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.


© 2020  American Academy of Allergy, Asthma & Immunology. Pubblicato da Elsevier Masson SAS. Tutti i diritti riservati.
Aggiungere alla mia biblioteca Togliere dalla mia biblioteca Stampare
Esportazione

    Citazioni Export

  • File

  • Contenuto

Vol 147 - N° 2

P. 677 - Febbraio 2021 Ritorno al numero
Articolo precedente Articolo precedente
  • Altered chromatin landscape in circulating T follicular helper and regulatory cells following grass pollen subcutaneous and sublingual immunotherapy
  • Hanisah Sharif, Swati Acharya, Gopal Krishna R. Dhondalay, Gilda Varricchi, Shoshanna Krasner-Macleod, Wannada Laisuan, Amy Switzer, Madison Lenormand, Elena Kashe, Rebecca V. Parkin, Yi Yi, Merve Koc, Oleksandra Fedina, Gemma Vilà-Nadal, Gianni Marone, Aarif Eifan, Guy W. Scadding, David J. Fear, Kari C. Nadeau, Stephen R. Durham, Mohamed H. Shamji
| Articolo seguente Articolo seguente
  • Bronchoalveolar lavage cytokine patterns in children with severe neutrophilic and paucigranulocytic asthma
  • John W. Steinke, Monica G. Lawrence, W. Gerald Teague, Thomas J. Braciale, James T. Patrie, Larry Borish

Benvenuto su EM|consulte, il riferimento dei professionisti della salute.
L'accesso al testo integrale di questo articolo richiede un abbonamento.

Già abbonato a @@106933@@ rivista ?

Il mio account


Dichiarazione CNIL

EM-CONSULTE.COM è registrato presso la CNIL, dichiarazione n. 1286925.

Ai sensi della legge n. 78-17 del 6 gennaio 1978 sull'informatica, sui file e sulle libertà, Lei puo' esercitare i diritti di opposizione (art.26 della legge), di accesso (art.34 a 38 Legge), e di rettifica (art.36 della legge) per i dati che La riguardano. Lei puo' cosi chiedere che siano rettificati, compeltati, chiariti, aggiornati o cancellati i suoi dati personali inesati, incompleti, equivoci, obsoleti o la cui raccolta o di uso o di conservazione sono vietati.
Le informazioni relative ai visitatori del nostro sito, compresa la loro identità, sono confidenziali.
Il responsabile del sito si impegna sull'onore a rispettare le condizioni legali di confidenzialità applicabili in Francia e a non divulgare tali informazioni a terzi.


Tutto il contenuto di questo sito: Copyright © 2024 Elsevier, i suoi licenziatari e contributori. Tutti i diritti sono riservati. Inclusi diritti per estrazione di testo e di dati, addestramento dell’intelligenza artificiale, e tecnologie simili. Per tutto il contenuto ‘open access’ sono applicati i termini della licenza Creative Commons.