A causal effects of neutrophil extracellular traps and its biomarkers on acute respiratory distress syndrome: a two-sample Mendelian randomization study.
Summary
Two-sample Mendelian randomization indicates a causal association between genetically predicted IL-13 levels and increased ARDS risk (OR 1.52). Other NETs-related biomarkers showed no causal effect, and reverse causality from ARDS to NETs traits was not supported. Sensitivity analyses found no substantial pleiotropy, heterogeneity, or outliers.
Key Findings
- Genetically predicted IL-13 increases ARDS risk (OR 1.52, 95% CI 1.03–2.23; P=0.047).
- No causal effects of other NETs-related biomarkers on ARDS (all P>0.05).
- No evidence for reverse causation from ARDS to NETs traits (all P>0.05).
- Sensitivity analyses (MR-Egger, MR-PRESSO, Cochran’s Q, leave-one-out) showed no pleiotropy, heterogeneity, or dominant instruments.
Clinical Implications
IL-13 may be a viable target for therapeutic modulation and a candidate biomarker for ARDS susceptibility. Translation will require mechanistic validation and trials testing IL-13–directed interventions and clinical assays.
Why It Matters
This is among the first genetic causal analyses linking IL-13 to ARDS, elevating IL-13 from an associative to a putative causal mediator. It prioritizes IL-13 as a therapeutic target and risk stratification biomarker.
Limitations
- Abstract does not specify GWAS sources, ancestry, or sample sizes, limiting generalizability assessment.
- Borderline statistical significance (P=0.047) and reliance on genetic proxies warrant cautious interpretation and replication.
Future Directions
Validate IL-13 causality with mechanistic studies, multi-ancestry MR, and prospective cohorts; evaluate IL-13–targeted therapies and clinical assays in interventional trials.
Study Information
- Study Type
- Case-control
- Research Domain
- Pathophysiology
- Evidence Level
- III - Observational genetic instrumental variable analysis using two-sample MR from GWAS summary data.
- Study Design
- OTHER