Circulating inflammatory proteins as causal drivers and therapeutic targets in asthma: insights from genetic and pathway-based analyses
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background Chronic inflammation plays a central role in asthma pathogenesis, but the causal contributions of specific circulating inflammatory proteins remain unclear. Here, we integrate genetic and pathway-based analyses to identify inflammatory proteins that may drive asthma development and serve as therapeutic targets.Methods We used genetically anchored instrumental variables from 180 protein quantitative trait loci (pQTLs) to assess the causal effects of 91 circulating inflammatory proteins on asthma risk, using large-scale GWAS datasets. Analytical robustness was evaluated through pleiotropy and heterogeneity testing. Functional enrichment and literature-based pathway analyses were performed to support biological plausibility and validate findings.Results Four proteins showed significant causal effects on asthma: CCL19 and LIFR were protective (OR = 0.89 and 0.91, p ≤ 6.8E-03), while ARTN and IL6 were associated with increased risk (OR = 1.15 and 1.18, p ≤ 1.1E-04). We also identified reverse causal effects of asthma on 11 cytokines, including MMP10, TGFB1, IL33, and IL18R1. Most of these proteins were enriched in pathways related to cytokine signaling and immune response (p < 0.001). All identified proteins had prior literature support linking them to asthma or airway inflammation.Conclusions Our findings highlight a subset of circulating inflammatory proteins that are likely causal in asthma pathogenesis and may serve as promising targets for therapeutic intervention. These results offer novel insights into the immunological mechanisms underlying asthma and support the utility of genetic causal inference in target prioritization.
Source: Journal of Asthma
Authors: Yiyan Miao, Haihua Chen, Qishu Wei, Kun Yan, Praise Audax Rukonge, Zhe Zhang, Guiping Yu
Institution: Xuzhou Medical College
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4413866427