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

doi:10.1038/s41467-024-48507-7

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

Nat Commun. 2024 May 28;15(1):4546. doi: 10.1038/s41467-024-48507-7.

Authors

Brooke Szczesny^#¹, Meher Preethi Boorgula^#², Sameer Chavan³, Monica Campbell³, Randi K Johnson^{4

5}, Kai Kammers⁶, Emma E Thompson⁷, Madison S Cox⁷, Gautam Shankar¹, Corey Cox², Andréanne Morin⁶, Wendy Lorizio¹, Michelle Daya², Samir N P Kelada^{8

9}, Terri H Beaty¹⁰, Ayo P Doumatey¹¹, Alvaro A Cruz¹², Harold Watson¹³, Edward T Naureckas¹⁴, B Louise Giles¹⁵, Ganiyu A Arinola¹⁶, Olumide Sogaolu¹⁷, Adegoke G Falade¹⁸, Nadia N Hansel¹, Ivana V Yang¹⁹, Christopher O Olopade²⁰, Charles N Rotimi¹¹, R Clive Landis²¹, Camila A Figueiredo^{22

23}, Matthew C Altman^{24

25}, Eimear Kenny²⁶, Ingo Ruczinski²⁷, Andrew H Liu²⁸, Carole Ober⁶, Margaret A Taub²⁷, Kathleen C Barnes²⁹, Rasika A Mathias³⁰

Affiliations

¹ Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
² Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.
³ Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁴ Department of Epidemiology, Colorado School of Public Health, Aurora, CO, USA.
⁵ Quantitative Sciences Division, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ Departments of Human Genetics, University of Chicago, Chicago, IL, USA.
⁷ Division of Allergy and Infectious Diseases, Dept of Medicine, University of Washington, Seattle, WA, USA.
⁸ Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
⁹ Marsico Lung Institute, University of North Carolina, Chapel Hill, NC, USA.
¹⁰ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
¹¹ Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
¹² Fundacao ProAR and Federal University of Bahia, Salvador, Bahia, Brazil.
¹³ Faculty of Medical Sciences, The University of the West Indies, Queen Elizabeth Hospital, St. Michael, Bridgetown, Barbados.
¹⁴ Departments of Medicine, University of Chicago, Chicago, IL, USA.
¹⁵ Departments of Pediatrics, University of Chicago, Chicago, IL, USA.
¹⁶ Department of Immunology, College of Medicine, University of Ibadan, Ibadan, Nigeria.
¹⁷ Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria.
¹⁸ Department of Pediatrics, University of Ibadan, and University College Hospital, Ibadan, Nigeria.
¹⁹ Departments of Biomedical Informatics and Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.
²⁰ Department of Medicine, University of Chicago, Chicago, IL, USA.
²¹ 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, Wanstead, Barbados.
²² Federal University of Bahia and Funda. Program for Control of Asthma in Bahia (ProAR), Salvador, Brazil.
²³ Instituto de Ciências de Saúde, Universidade Federal da Bahia, Salvador, Brazil.
²⁴ Systems Immunology Program, Benaroya Research Institute, Seattle, WA, 98101, USA.
²⁵ Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, 98109, USA.
²⁶ Center for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
²⁷ Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
²⁸ Department of Pediatrics, Childrens Hospital Colorado and University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.
²⁹ Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA. kathleen.barnes@cuanschutz.edu.
³⁰ Department of Medicine, Johns Hopkins University, Baltimore, MD, USA. rmathias@jhmi.edu.

^# Contributed equally.

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.

MeSH terms

Adult
Asthma* / genetics
Asthma* / metabolism
Black People* / genetics
Case-Control Studies
DNA Methylation*
Female
Fibronectins / genetics
Fibronectins / metabolism
Gene Expression Regulation
Gene Regulatory Networks
Humans
Male
Middle Aged
Multiomics
Nasal Mucosa* / metabolism
Tacrolimus Binding Proteins* / genetics
Tacrolimus Binding Proteins* / metabolism

Substances

Tacrolimus Binding Proteins
tacrolimus binding protein 5
Fibronectins

Abstract

MeSH terms

Substances

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