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Multi-omics in nasal epithelium reveals three axes of dysregulation for asthma risk in the African Diaspora populations

Author

Listed:
  • Brooke Szczesny

    (Johns Hopkins University)

  • Meher Preethi Boorgula

    (Anschutz Medical Campus)

  • Sameer Chavan

    (University of Colorado Anschutz Medical Campus)

  • Monica Campbell

    (University of Colorado Anschutz Medical Campus)

  • Randi K. Johnson

    (Colorado School of Public Health
    Johns Hopkins University School of Medicine)

  • Kai Kammers

    (University of Chicago)

  • Emma E. Thompson

    (University of Washington)

  • Madison S. Cox

    (University of Washington)

  • Gautam Shankar

    (Johns Hopkins University)

  • Corey Cox

    (Anschutz Medical Campus)

  • Andréanne Morin

    (University of Chicago)

  • Wendy Lorizio

    (Johns Hopkins University)

  • Michelle Daya

    (Anschutz Medical Campus)

  • Samir N. P. Kelada

    (University of North Carolina
    University of North Carolina)

  • Terri H. Beaty

    (Johns Hopkins Bloomberg School of Public Health)

  • Ayo P. Doumatey

    (National Institutes of Health)

  • Alvaro A. Cruz

    (Fundacao ProAR and Federal University of Bahia)

  • Harold Watson

    (Queen Elizabeth Hospital)

  • Edward T. Naureckas

    (University of Chicago)

  • B. Louise Giles

    (University of Chicago)

  • Ganiyu A. Arinola

    (College of Medicine, University of Ibadan)

  • Olumide Sogaolu

    (College of Medicine, University of Ibadan)

  • Adegoke G. Falade

    (University of Ibadan, and University College Hospital)

  • Nadia N. Hansel

    (Johns Hopkins University)

  • Ivana V. Yang

    (University of Colorado Denver, Anschutz Medical Campus)

  • Christopher O. Olopade

    (University of Chicago)

  • Charles N. Rotimi

    (National Institutes of Health)

  • R. Clive Landis

    (Cave Hill Campus)

  • Camila A. Figueiredo

    (Federal University of Bahia and Funda. Program for Control of Asthma in Bahia (ProAR)
    Universidade Federal da Bahia)

  • Matthew C. Altman

    (Benaroya Research Institute
    University of Washington)

  • Eimear Kenny

    (Icahn School of Medicine at Mount Sinai)

  • Ingo Ruczinski

    (Johns Hopkins Bloomberg School of Public Health)

  • Andrew H. Liu

    (Childrens Hospital Colorado and University of Colorado Denver, Anschutz Medical Campus)

  • Carole Ober

    (University of Chicago)

  • Margaret A. Taub

    (Johns Hopkins Bloomberg School of Public Health)

  • Kathleen C. Barnes

    (Anschutz Medical Campus)

  • Rasika A. Mathias

    (Johns Hopkins University)

Abstract

Asthma has striking disparities across ancestral groups, but the molecular underpinning of these differences is poorly understood and minimally studied. A goal of the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to understand multi-omic signatures of asthma focusing on populations of African ancestry. RNASeq and DNA methylation data are generated from nasal epithelium including cases (current asthma, N = 253) and controls (never-asthma, N = 283) from 7 different geographic sites to identify differentially expressed genes (DEGs) and gene networks. We identify 389 DEGs; the top DEG, FN1, was downregulated in cases (q = 3.26 × 10−9) and encodes fibronectin which plays a role in wound healing. The top three gene expression modules implicate networks related to immune response (CEACAM5; p = 9.62 × 10−16 and CPA3; p = 2.39 × 10−14) and wound healing (FN1; p = 7.63 × 10−9). Multi-omic analysis identifies FKBP5, a co-chaperone of glucocorticoid receptor signaling known to be involved in drug response in asthma, where the association between nasal epithelium gene expression is likely regulated by methylation and is associated with increased use of inhaled corticosteroids. This work reveals molecular dysregulation on three axes – increased Th2 inflammation, decreased capacity for wound healing, and impaired drug response – that may play a critical role in asthma within the African Diaspora.

Suggested Citation

  • Brooke Szczesny & Meher Preethi Boorgula & Sameer Chavan & Monica Campbell & Randi K. Johnson & Kai Kammers & Emma E. Thompson & Madison S. Cox & Gautam Shankar & Corey Cox & Andréanne Morin & Wendy L, 2024. "Multi-omics in nasal epithelium reveals three axes of dysregulation for asthma risk in the African Diaspora populations," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48507-7
    DOI: 10.1038/s41467-024-48507-7
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    References listed on IDEAS

    as
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