Investigating the potential of oxidative stress-related gene as predictive markers in idiopathic pulmonary fibrosis

Abstract This study investigates genes linking oxidative stress to idiopathic pulmonary fibrosis (IPF) through multi-omics data integration. We collected oxidative stress-related genes from GeneCards and integrated data for gene expression (eQTLs), DNA methylation (mQTLs), and protein expression (pQ...

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Main Authors: Yuhao Wang, Zhao Zhang, Hongnan Zhang, Luyao Xu, Shuling Huang, Ying Wen, Zhiming Zhuang, Xiaoxin Li, Jinyi Lu, Xudong Li
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-02579-7
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Summary:Abstract This study investigates genes linking oxidative stress to idiopathic pulmonary fibrosis (IPF) through multi-omics data integration. We collected oxidative stress-related genes from GeneCards and integrated data for gene expression (eQTLs), DNA methylation (mQTLs), and protein expression (pQTLs). Genome-wide association study (GWAS) data on IPF from Allen et al. served as the discovery set, with FinnGen R10 for validation. Summary data-based Mendelian randomization (SMR) and colocalization analyses assessed interactions and shared causal variants, followed by multi-omics integration with tissue-specific validation. SMR and colocalization screening identified 90 mQTLs, 15 eQTLs, and 2 pQTLs (KRT18 and FOXO1) linked to IPF in the discovery cohort. Twelve mQTLs were validated in the FinnGen cohort, with MUC1 showing strong SMR and colocalization evidence (eQTL). Multi-omics integration validated NDUFA9 (mQTL-eQTL) level and FOXO1 (mQTL-eQTL-pQTL). Our study identified key oxidative stress-related genes (i.e., FOXO1 and NDUFA9) in IPF pathogenesis, highlighting the need for further research to inform prevention and treatment.
ISSN:2045-2322