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Updated: May 14, 2026
Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
Genetically Predicted Serum miRNAs as Potential Causal Drivers of Atopic Dermatitis: Evidence from Large-Scale GWAS
1Department of Dermatology, Ningbo Haishu People's Hospital, Ningbo, Zhejiang, 315000, People's Republic of China.
Background:
Although dysregulated microRNAs (miRNAs) are implicated in Atopic Dermatitis (AD), their causal roles remain elusive due to potential confounding and reverse causation. We aimed to systematically identify causal miRNAs for AD and elucidate their underlying mechanisms.
Methods:
We conducted a bidirectional two-sample Mendelian randomization (MR) study using large-scale GWAS summary statistics for 2083 miRNAs and AD. The findings were validated using independent trans- and cis-eQTL datasets, and consistency was assessed via correlation analysis. Bayesian colocalization was applied to distinguish pleiotropy from linkage disequilibrium. Downstream targets were analyzed via GO/KEGG enrichment, and clinical relevance was verified using differential expression analysis in two independent patient cohorts (GSE162926 and GSE217232).
Results:
We identified six circulatory miRNAs causally associated with AD. Notably, miR-1908-5p, miR-148a-3p, miR-133a-3p were identified as a robust risk factor, while miR-125a-5p, miR-181b-5p, let-7e-5p exhibited a protective effect. Colocalization analysis revealed compelling evidence (PP.H4=0.99) for a shared causal variant (rs174561) between miR-1908-5p and AD. Reverse MR indicated no causal effect of AD on these miRNAs. Functional enrichment analyses revealed that downstream targets were predominantly enriched in the PI3K-Akt and MAPK signaling pathways, regulating biological processes critical for skin barrier integrity, wound healing, and oxidative stress response. Crucially, transcriptomic analysis in clinical cohorts corroborated the MR findings, showing significant dysregulation of the identified miRNAs in AD patients.
Conclusion:
This study provides robust genetic and transcriptomic evidence for the causal involvement of specific circulating miRNAs, particularly miR-1908-5p, in AD pathogenesis. These findings offer potential novel biomarkers and therapeutic targets for precision medicine in AD.
Insights
This study identified causal microRNAs (miRNAs) linked to atopic dermatitis (AD). Specific miRNAs like miR-1908-5p are risk factors, while others offer protection, suggesting new diagnostic and therapeutic avenues for AD.
Area of Science:
- Genetics
- Molecular Biology
- Dermatology
Background:
- MicroRNAs (miRNAs) are implicated in atopic dermatitis (AD) pathogenesis.
- Causal roles of miRNAs in AD remain unclear due to confounding factors.
- Systematic identification of causal miRNAs and their mechanisms in AD is needed.
Purpose of the Study:
- To systematically identify causal microRNAs (miRNAs) associated with atopic dermatitis (AD).
- To elucidate the underlying molecular mechanisms of identified causal miRNAs in AD.
- To validate findings using genetic and clinical data for potential therapeutic targets.
Main Methods:
- Bidirectional two-sample Mendelian randomization (MR) using large-scale GWAS data for 2083 miRNAs and AD.
- Validation with independent trans- and cis-eQTL datasets and correlation analysis.
- Bayesian colocalization, GO/KEGG enrichment, and differential expression analysis in patient cohorts.
Main Results:
- Six circulatory miRNAs were causally associated with AD; miR-1908-5p, miR-148a-3p, miR-133a-3p (risk), and miR-125a-5p, miR-181b-5p, let-7e-5p (protective).
- Strong evidence for shared causal variant (rs174561) between miR-1908-5p and AD; no reverse causation from AD to miRNAs.
- Downstream targets involve PI3K-Akt and MAPK pathways crucial for skin barrier function; transcriptomic data confirmed miRNA dysregulation in AD patients.
Conclusions:
- Robust genetic and transcriptomic evidence supports the causal role of specific circulating miRNAs, notably miR-1908-5p, in atopic dermatitis pathogenesis.
- Identified miRNAs represent potential novel biomarkers for AD diagnosis.
- These miRNAs may serve as therapeutic targets for precision medicine approaches in AD treatment.
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