Abstract
Background: Allergic asthma (AA) is a chronic inflammatory disease with limited effective treatments, often co-occurring with atopic dermatitis (AD). Epidemiologic studies have shown a strong association between AD and AA, but their causal relationship remains unclear.
Objectives: This study aimed to identify novel therapeutic targets and candidate drugs for AA.
Methods: We performed Mendelian (MR) analysis to evaluate the causal relationship between AD and AA. To identify potential therapeutic targets, we integrated drug-target MR, colocalization, functional enrichment, protein–protein interaction, and gene expression analyses. Drug candidates were prioritized using the Drug–Gene Interaction Database (DGIdb; dgidb.org) and the Comparative Toxicogenomics Database (CTD; ctdbase.org).
Results: MR analysis confirmed that AD significantly increases the risk of AA (odds ratio = 1.64, P < .001). Integrating drug-target MR and colocalization analysis, we identified Janus kinase 2 (JAK2) as a potential causal gene (posterior probability [PP.H4] = 0.95), supported by functional enrichment, protein–protein interaction, and gene expression analyses. Drug screening via DGIdb and CTD prioritized hydroxyurea as the top candidate (composite score = 0.85), although its efficacy in AA remains to be validated.
Conclusions: We provide the first genomic evidence for a causal link between AD and AA. These findings highlight JAK2 as a potential therapeutic target and hydroxyurea as a candidate for clinical validation, paving the way for future research into shared immunogenetic mechanisms in allergic diseases.
© 2025 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology. This is an open access article under the CC BY-NC-ND license
Objectives: This study aimed to identify novel therapeutic targets and candidate drugs for AA.
Methods: We performed Mendelian (MR) analysis to evaluate the causal relationship between AD and AA. To identify potential therapeutic targets, we integrated drug-target MR, colocalization, functional enrichment, protein–protein interaction, and gene expression analyses. Drug candidates were prioritized using the Drug–Gene Interaction Database (DGIdb; dgidb.org) and the Comparative Toxicogenomics Database (CTD; ctdbase.org).
Results: MR analysis confirmed that AD significantly increases the risk of AA (odds ratio = 1.64, P < .001). Integrating drug-target MR and colocalization analysis, we identified Janus kinase 2 (JAK2) as a potential causal gene (posterior probability [PP.H4] = 0.95), supported by functional enrichment, protein–protein interaction, and gene expression analyses. Drug screening via DGIdb and CTD prioritized hydroxyurea as the top candidate (composite score = 0.85), although its efficacy in AA remains to be validated.
Conclusions: We provide the first genomic evidence for a causal link between AD and AA. These findings highlight JAK2 as a potential therapeutic target and hydroxyurea as a candidate for clinical validation, paving the way for future research into shared immunogenetic mechanisms in allergic diseases.
© 2025 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology. This is an open access article under the CC BY-NC-ND license
| Original language | English |
|---|---|
| Article number | 100568 |
| Journal | Journal of Allergy and Clinical Immunology: Global |
| Volume | 4 |
| Issue number | 4 |
| Online published | 23 Sept 2025 |
| DOIs | |
| Publication status | Published - Nov 2025 |
Funding
Supported by the City University of Hong Kong Internal Funds for External Grant Schemes (grant 9678233).
Research Keywords
- allergic asthma
- Atopic dermatitis
- genetic association
- Mendelian randomization
Publisher's Copyright Statement
- This full text is made available under CC-BY-NC-ND 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/
