Transcriptome-wide association study of sex effects identifies sex-specific nasal epithelial gene expression profiles for total IgE - 05/05/26
Abstract |
Background |
Asthma is the most common chronic respiratory disease in children, with known sex differences in prevalence and severity that shift after puberty. Total IgE, a marker of type 2–high asthma, also differs by sex and age and may contribute to these disparities.
Methods |
We tested whether nasal epithelial gene expression differs by sex and interacts with total IgE in ways that may inform asthma pathogenesis in a transcriptome-wide association study in nasal epithelial samples from participants in two cohorts: EVA-PR (including 398 Puerto Rican youths aged 12-20 years) and PIAMA (including 303 Dutch adolescents aged 16 years).
Results |
Differential expression analysis by sex identified 406 genes at a false discovery rate–adjusted P value of < .05, with 225 upregulated and 181 downregulated in female compared to male subjects. Top differentially expressed genes included hormone- and immune-related genes such as THRB, IL17REL, and CD207 . Among these, 6 genes ( MNDA, IFIT1, IFIT2, SLC22A17, JAG2, and MT3 ) showed significant sex-by-total IgE interaction effects on expression. Pathway enrichment analyses revealed that female subjects had activation of eukaryotic translation pathways (eg, EIF2 signaling), while male subjects showed activation of immune-related pathways (eg, interferon signaling). Additionally, 19 pathways were enriched in the sex-by-IgE interaction model, including TREM1 and cytokine storm signaling.
Conclusions |
Our findings provide new insights into sex-specific regulation of gene expression in airway epithelium and its interaction with total IgE, helping to explain observed sex differences in asthma. This underscores the need to consider sex as a biological variable in asthma research and points to potential targets for precision medicine approaches.
Le texte complet de cet article est disponible en PDF.Key words : TWAS, sex, total IgE, EVA-PR, PIAMA
Abbreviations used : DEG, EVA-PR, FDR, FDR-P, PIAMA, QC, RNA-Seq, T2, T17
Plan
| The first 2 authors contributed equally to this article, and both should be considered first author. The last 2 authors contributed equally to this article, and both should be considered senior author. |
Vol 157 - N° 5
P. 1043-1051 - mai 2026 Retour au numéro
Article précédent
- Disparities in asthma control and treatment: A spotlight on Mexican American children
- Khamron Micheals, Emily M. Hall, Sarah Chambliss, Susan Balcer-Whaley, Rebecca A. Zárate, Erin Rodriguez, Roger Peng, Darlene Bhavnani, Elizabeth C. Matsui
- Breast-feeding is inversely associated with asthma and IgE sensitization up to young adulthood
- Inger Kull, Maria Ödling, Niklas Andersson, Erik Melén, Sandra Ekström, Anna Bergström
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?