Multi-omics in nasal epithelium reveals three axes of dysregulation for asthma risk in the African Diaspora populations
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 as...
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Nature Portfolio
2024-05-01
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| Online Access: | https://doi.org/10.1038/s41467-024-48507-7 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Brooke Szczesny |
| collection | DOAJ |
| container_title | Nature Communications |
| description | 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. |
| format | Article |
| id | doaj-art-db1254fb2cdc4e4c8565e2404e6adbdb |
| institution | Directory of Open Access Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-05-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-db1254fb2cdc4e4c8565e2404e6adbdb2025-08-20T00:04:19ZengNature PortfolioNature Communications2041-17232024-05-0115111210.1038/s41467-024-48507-7Multi-omics in nasal epithelium reveals three axes of dysregulation for asthma risk in the African Diaspora populationsBrooke Szczesny0Meher Preethi Boorgula1Sameer Chavan2Monica Campbell3Randi K. Johnson4Kai Kammers5Emma E. Thompson6Madison S. Cox7Gautam Shankar8Corey Cox9Andréanne Morin10Wendy Lorizio11Michelle Daya12Samir N. P. Kelada13Terri H. Beaty14Ayo P. Doumatey15Alvaro A. Cruz16Harold Watson17Edward T. Naureckas18B. Louise Giles19Ganiyu A. Arinola20Olumide Sogaolu21Adegoke G. Falade22Nadia N. Hansel23Ivana V. Yang24Christopher O. Olopade25Charles N. Rotimi26R. Clive Landis27Camila A. Figueiredo28Matthew C. Altman29Eimear Kenny30Ingo Ruczinski31Andrew H. Liu32Carole Ober33Margaret A. Taub34Kathleen C. Barnes35Rasika A. Mathias36Department of Medicine, Johns Hopkins UniversityDepartment of Medicine, University of Colorado Denver, Anschutz Medical CampusDepartment of Biomedical Informatics, University of Colorado Anschutz Medical CampusDepartment of Biomedical Informatics, University of Colorado Anschutz Medical CampusDepartment of Epidemiology, Colorado School of Public HealthDepartments of Human Genetics, University of ChicagoDivision of Allergy and Infectious Diseases, Dept of Medicine, University of WashingtonDivision of Allergy and Infectious Diseases, Dept of Medicine, University of WashingtonDepartment of Medicine, Johns Hopkins UniversityDepartment of Medicine, University of Colorado Denver, Anschutz Medical CampusDepartments of Human Genetics, University of ChicagoDepartment of Medicine, Johns Hopkins UniversityDepartment of Medicine, University of Colorado Denver, Anschutz Medical CampusDepartment of Genetics, University of North CarolinaDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public HealthCenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of HealthFundacao ProAR and Federal University of BahiaFaculty of Medical Sciences, The University of the West Indies, Queen Elizabeth HospitalDepartments of Medicine, University of ChicagoDepartments of Pediatrics, University of ChicagoDepartment of Immunology, College of Medicine, University of IbadanDepartment of Medicine, College of Medicine, University of IbadanDepartment of Pediatrics, University of Ibadan, and University College HospitalDepartment of Medicine, Johns Hopkins UniversityDepartments of Biomedical Informatics and Medicine, University of Colorado Denver, Anschutz Medical CampusDepartment of Medicine, University of ChicagoCenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of HealthEdmund Cohen Laboratory for Vascular Research, George Alleyne Chronic Disease Research Centre, Caribbean Institute for Health Research, The University of the West Indies, Cave Hill CampusFederal University of Bahia and Funda. Program for Control of Asthma in Bahia (ProAR)Systems Immunology Program, Benaroya Research InstituteCenter for Genomic Health, Icahn School of Medicine at Mount SinaiDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public HealthDepartment of Pediatrics, Childrens Hospital Colorado and University of Colorado Denver, Anschutz Medical CampusDepartments of Human Genetics, University of ChicagoDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public HealthDepartment of Medicine, University of Colorado Denver, Anschutz Medical CampusDepartment of Medicine, Johns Hopkins UniversityAbstract 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.https://doi.org/10.1038/s41467-024-48507-7 |
| spellingShingle | 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 Multi-omics in nasal epithelium reveals three axes of dysregulation for asthma risk in the African Diaspora populations |
| title | Multi-omics in nasal epithelium reveals three axes of dysregulation for asthma risk in the African Diaspora populations |
| title_full | Multi-omics in nasal epithelium reveals three axes of dysregulation for asthma risk in the African Diaspora populations |
| title_fullStr | Multi-omics in nasal epithelium reveals three axes of dysregulation for asthma risk in the African Diaspora populations |
| title_full_unstemmed | Multi-omics in nasal epithelium reveals three axes of dysregulation for asthma risk in the African Diaspora populations |
| title_short | Multi-omics in nasal epithelium reveals three axes of dysregulation for asthma risk in the African Diaspora populations |
| title_sort | multi omics in nasal epithelium reveals three axes of dysregulation for asthma risk in the african diaspora populations |
| url | https://doi.org/10.1038/s41467-024-48507-7 |
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