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

• Published in: Nature communications 2024-05, Vol.15 (1), p.4546-12, Article 4546
• Main Authors: 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.
• Format: Article
• Language: English
• Subjects: 38/91; 631/208/176; 631/208/199; 631/208/212/2019; Adult; Asthma; Asthma - genetics; Asthma - metabolism; Black People - genetics; Case-Control Studies; Corticoids; Corticosteroids; Deoxyribonucleic acid; Diaspora; DNA; DNA Methylation; Down-regulation; Epithelium; Female; Fibronectin; Fibronectins - genetics; Fibronectins - metabolism; Gene expression; Gene Expression Regulation; Gene Regulatory Networks; Glucocorticoid receptors; Glucocorticoids; Health risks; Humanities and Social Sciences; Humans; Immune response; Lymphocytes T; Male; Middle Aged; multidisciplinary; Multiomics; Nasal Mucosa - metabolism; Populations; Science; Science (multidisciplinary); Tacrolimus Binding Proteins - genetics; Tacrolimus Binding Proteins - metabolism; Wound healing
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-48507-7

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. Here, the authors suggest that molecular dysregulation on three axes may play a critical role in asthma within the African Diaspora. RNASeq and DNA methylation data are generated from nasal epithelium including cases and controls from seven different geographic sites.