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. 2025 Jul;24(7):e70334.
doi: 10.1111/jocd.70334.

Integrated Genomic and GEO Data Analysis Reveals Therapeutic Targets for Rosacea

Xinrui Deng  1 , Sui He  1 , Huiyu Long  2 , Jinyuan Xiao  1 , Zhengchun Xie  1
Affiliations

Integrated Genomic and GEO Data Analysis Reveals Therapeutic Targets for Rosacea

Xinrui Deng et al. J Cosmet Dermatol. 2025 Jul.

Abstract

Background: Rosacea is a chronic inflammatory facial disorder with limited therapeutic options, severely impacting patients' quality of life. The identification of druggable genes plays a crucial role in facilitating the development of effective therapeutic strategies.

Methods: We conducted Mendelian randomization (MR) and Summary-based Mendelian randomization (SMR) analyses by integrating data on 5883 druggable genes, cis-expressed quantitative trait loci (eQTL) from blood and skin tissue (lower leg and suprapubic), and genome-wide association study (GWAS) data on rosacea to elucidate the causal relationship between druggable genes and rosacea. Robustness was confirmed via heterogeneity/horizontal pleiotropy tests, Steiger filtering, Bayesian colocalization analysis, and the heterogeneity in dependent instruments (HEIDI) analysis. The expression levels of identified druggable genes were validated using the GSE65914 data sets. Further analyses included protein-protein interactions (PPIs), functional enrichment analysis, phenome-wide association study (PheWAS), drug prediction, and molecular docking.

Results: MR and SMR analyses identified IRF1 and SLC22A5 as druggable genes for rosacea, with Bayesian colocalization strongly supporting shared causal variants. GEO data sets confirmed significant upregulation of IRF1 and downregulation of SLC22A5 in rosacea patients. PPIs and functional enrichment analyses revealed that IRF1 promotes inflammation by regulating immune cell activation and interferon signaling pathways; SLC22A5 regulates membrane transport and metabolic processes, and its dysregulation may lead to lipid homeostasis imbalance. PheWAS analysis indicated no other phenotypes associated with IRF1 and SLC22A5. Drug prediction and molecular docking verified the pharmacological value of IRF1 and SLC22A5.

Conclusion: This study identified IRF1 and SLC22A5 as potential drug targets for the treatment of rosacea, and their significant therapeutic potential provides a critical foundation for the development of targeted therapies.

Keywords: GWAS; IRF1; SLC22A5; druggable genes; mendelian randomization; rosacea.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Overview of study design to identify drug targets for rosacea (created with Biorender.com).
FIGURE 2
FIGURE 2
Significant MR analysis results. CI, confidence interval; IVW, inverse variance weighted; nonsun‐exposed, sun‐not‐exposed suprapubic skin; SNP, single nucleotide polymorphism; sun‐exposed, sun‐exposed skin of the lower leg.
FIGURE 3
FIGURE 3
Expression levels of IRF1 and SLC22A5 in rosacea. (A) IRF in ETR (B) SLC22A5 in ETR (C) IRF in PPR (D) SLC22A5 in PPR (E) IRF in PhR (F) SLC22A5 in PhR ETR, Erythematotelangiectasia rosacea; PhR, Phymatous rosacea; PPR, Papulopustular rosacea.
FIGURE 4
FIGURE 4
PPI analysis and GO function enrichment analysis. (A) GeneMANIA gene network of IRF1 (B) GeneMANIA gene network of SLC22A5 (C) GO functional enrichment analysis for IRF1‐centered network (D) GO functional enrichment analysis for SLC22A5‐centered network.
FIGURE 5
FIGURE 5
Docking results of available proteins small molecules. (A) IRF1 with Tretinoin, (B) IRF1 with Cephaeline, (C) IRF1 with Amiodarone, (D) IRF1 with Emetine, (E) SLC22A5 with Tretinoin, (F) SLC22A5 with Cephaeline, (G) SLC22A5 with Amiodarone, (H) SLC22A5 with Emetine.
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