Nature Communications (May 2024)
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,
- Rasika A. Mathias
Affiliations
- Brooke Szczesny
- Department of Medicine, Johns Hopkins University
- Meher Preethi Boorgula
- Department of Medicine, University of Colorado Denver, Anschutz Medical Campus
- Sameer Chavan
- Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus
- Monica Campbell
- Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus
- Randi K. Johnson
- Department of Epidemiology, Colorado School of Public Health
- Kai Kammers
- Departments of Human Genetics, University of Chicago
- Emma E. Thompson
- Division of Allergy and Infectious Diseases, Dept of Medicine, University of Washington
- Madison S. Cox
- Division of Allergy and Infectious Diseases, Dept of Medicine, University of Washington
- Gautam Shankar
- Department of Medicine, Johns Hopkins University
- Corey Cox
- Department of Medicine, University of Colorado Denver, Anschutz Medical Campus
- Andréanne Morin
- Departments of Human Genetics, University of Chicago
- Wendy Lorizio
- Department of Medicine, Johns Hopkins University
- Michelle Daya
- Department of Medicine, University of Colorado Denver, Anschutz Medical Campus
- Samir N. P. Kelada
- Department of Genetics, University of North Carolina
- Terri H. Beaty
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health
- Ayo P. Doumatey
- Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health
- Alvaro A. Cruz
- Fundacao ProAR and Federal University of Bahia
- Harold Watson
- Faculty of Medical Sciences, The University of the West Indies, Queen Elizabeth Hospital
- Edward T. Naureckas
- Departments of Medicine, University of Chicago
- B. Louise Giles
- Departments of Pediatrics, University of Chicago
- Ganiyu A. Arinola
- Department of Immunology, College of Medicine, University of Ibadan
- Olumide Sogaolu
- Department of Medicine, College of Medicine, University of Ibadan
- Adegoke G. Falade
- Department of Pediatrics, University of Ibadan, and University College Hospital
- Nadia N. Hansel
- Department of Medicine, Johns Hopkins University
- Ivana V. Yang
- Departments of Biomedical Informatics and Medicine, University of Colorado Denver, Anschutz Medical Campus
- Christopher O. Olopade
- Department of Medicine, University of Chicago
- Charles N. Rotimi
- Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health
- R. Clive Landis
- Edmund Cohen Laboratory for Vascular Research, George Alleyne Chronic Disease Research Centre, Caribbean Institute for Health Research, The University of the West Indies, Cave Hill Campus
- Camila A. Figueiredo
- Federal University of Bahia and Funda. Program for Control of Asthma in Bahia (ProAR)
- Matthew C. Altman
- Systems Immunology Program, Benaroya Research Institute
- Eimear Kenny
- Center for Genomic Health, Icahn School of Medicine at Mount Sinai
- Ingo Ruczinski
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health
- Andrew H. Liu
- Department of Pediatrics, Childrens Hospital Colorado and University of Colorado Denver, Anschutz Medical Campus
- Carole Ober
- Departments of Human Genetics, University of Chicago
- Margaret A. Taub
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health
- Kathleen C. Barnes
- Department of Medicine, University of Colorado Denver, Anschutz Medical Campus
- Rasika A. Mathias
- Department of Medicine, Johns Hopkins University
- DOI
- https://doi.org/10.1038/s41467-024-48507-7
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 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.
