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

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 Lorizio, Michelle Daya, Samir N. P. Kelada, Terri H. Beaty, Ayo P. Doumatey, Alvaro A. Cruz, Harold Watson, Edward T. Naureckas, B. Louise Giles, Ganiyu A. Arinola, Olumide Sogaolu, Adegoke G. Falade, Nadia N. Hansel, Ivana V. Yang, Christopher O. Olopade, Charles N. Rotimi, R. Clive Landis, Camila A. Figueiredo, Matthew C. Altman, Eimear Kenny, Ingo Ruczinski, Andrew H. Liu, Carole Ober, Margaret A. Taub, Kathleen C. Barnes () and Rasika A. Mathias ()
Additional contact information
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
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
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)
Matthew C. Altman: Benaroya Research Institute
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

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-48507-7

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