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Multi-omics in nasal epithelium reveals three axes of dysregulation for asthma risk in the African Diaspora populations.
Szczesny, Brooke; Boorgula, Meher Preethi; Chavan, Sameer; Campbell, Monica; Johnson, Randi K; Kammers, Kai; Thompson, Emma E; Cox, Madison S; Shankar, Gautam; Cox, Corey; Morin, Andréanne; Lorizio, Wendy; Daya, Michelle; Kelada, Samir N P; Beaty, Terri H; Doumatey, Ayo P; Cruz, Alvaro A; Watson, Harold; Naureckas, Edward T; Giles, B Louise; Arinola, Ganiyu A; Sogaolu, Olumide; Falade, Adegoke G; Hansel, Nadia N; Yang, Ivana V; Olopade, Christopher O; Rotimi, Charles N; Landis, R Clive; Figueiredo, Camila A; Altman, Matthew C; Kenny, Eimear; Ruczinski, Ingo; Liu, Andrew H; Ober, Carole; Taub, Margaret A; Barnes, Kathleen C; Mathias, Rasika A.
Afiliação
  • Szczesny B; Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • Boorgula MP; Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.
  • Chavan S; Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
  • Campbell M; Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
  • Johnson RK; Department of Epidemiology, Colorado School of Public Health, Aurora, CO, USA.
  • Kammers K; Quantitative Sciences Division, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Thompson EE; Departments of Human Genetics, University of Chicago, Chicago, IL, USA.
  • Cox MS; Division of Allergy and Infectious Diseases, Dept of Medicine, University of Washington, Seattle, WA, USA.
  • Shankar G; Division of Allergy and Infectious Diseases, Dept of Medicine, University of Washington, Seattle, WA, USA.
  • Cox C; Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • Morin A; Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.
  • Lorizio W; Departments of Human Genetics, University of Chicago, Chicago, IL, USA.
  • Daya M; Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • Kelada SNP; Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.
  • Beaty TH; Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
  • Doumatey AP; Marsico Lung Institute, University of North Carolina, Chapel Hill, NC, USA.
  • Cruz AA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Watson H; Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Naureckas ET; Fundacao ProAR and Federal University of Bahia, Salvador, Bahia, Brazil.
  • Giles BL; Faculty of Medical Sciences, The University of the West Indies, Queen Elizabeth Hospital, St. Michael, Bridgetown, Barbados.
  • Arinola GA; Departments of Medicine, University of Chicago, Chicago, IL, USA.
  • Sogaolu O; Departments of Pediatrics, University of Chicago, Chicago, IL, USA.
  • Falade AG; Department of Immunology, College of Medicine, University of Ibadan, Ibadan, Nigeria.
  • Hansel NN; Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria.
  • Yang IV; Department of Pediatrics, University of Ibadan, and University College Hospital, Ibadan, Nigeria.
  • Olopade CO; Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • Rotimi CN; Departments of Biomedical Informatics and Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.
  • Landis RC; Department of Medicine, University of Chicago, Chicago, IL, USA.
  • Figueiredo CA; Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Altman MC; 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.
  • Kenny E; Federal University of Bahia and Funda. Program for Control of Asthma in Bahia (ProAR), Salvador, Brazil.
  • Ruczinski I; Instituto de Ciências de Saúde, Universidade Federal da Bahia, Salvador, Brazil.
  • Liu AH; Systems Immunology Program, Benaroya Research Institute, Seattle, WA, 98101, USA.
  • Ober C; Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, 98109, USA.
  • Taub MA; Center for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Barnes KC; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Mathias RA; Department of Pediatrics, Childrens Hospital Colorado and University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.
Nat Commun ; 15(1): 4546, 2024 May 28.
Article em En | MEDLINE | ID: mdl-38806494
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Asma / Metilação de DNA / Proteínas de Ligação a Tacrolimo / População Negra / Mucosa Nasal Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Asma / Metilação de DNA / Proteínas de Ligação a Tacrolimo / População Negra / Mucosa Nasal Idioma: En Ano de publicação: 2024 Tipo de documento: Article