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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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-02579-7 |
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| author | Yuhao Wang Zhao Zhang Hongnan Zhang Luyao Xu Shuling Huang Ying Wen Zhiming Zhuang Xiaoxin Li Jinyi Lu Xudong Li |
| author_facet | Yuhao Wang Zhao Zhang Hongnan Zhang Luyao Xu Shuling Huang Ying Wen Zhiming Zhuang Xiaoxin Li Jinyi Lu Xudong Li |
| author_sort | Yuhao Wang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-84d7646801204d5abedf9fd5b894e054 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-84d7646801204d5abedf9fd5b894e0542025-08-20T03:37:30ZengNature PortfolioScientific Reports2045-23222025-07-0115111210.1038/s41598-025-02579-7Investigating the potential of oxidative stress-related gene as predictive markers in idiopathic pulmonary fibrosisYuhao Wang0Zhao Zhang1Hongnan Zhang2Luyao Xu3Shuling Huang4Ying Wen5Zhiming Zhuang6Xiaoxin Li7Jinyi Lu8Xudong Li9Guangdong Research Center of Occupational Hygiene, Guangdong Province Hospital for Occupational Disease Prevention and TreatmentSchool of Public Health, Southern Medical UniversityLonggui Street Community Health Service Center, Baiyun DistricSchool of Public Health, Sun Yat-sen University School of Public Health, Guangzhou Medical UniversityGuangzhou Women and Children’s Medical Centre, Institute of Pediatrics, Guangzhou Medical UniversitySchool of Public Health, Southern Medical UniversitySchool of Public Health, Southern Medical UniversitySchool of Public Health, Southern Medical UniversityGuangdong Research Center of Occupational Hygiene, Guangdong Province Hospital for Occupational Disease Prevention and TreatmentAbstract 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.https://doi.org/10.1038/s41598-025-02579-7Oxidative stressIdiopathic pulmonary fibrosisMulti-omicsMendelian randomization analysisColocalization analysis |
| spellingShingle | Yuhao Wang Zhao Zhang Hongnan Zhang Luyao Xu Shuling Huang Ying Wen Zhiming Zhuang Xiaoxin Li Jinyi Lu Xudong Li Investigating the potential of oxidative stress-related gene as predictive markers in idiopathic pulmonary fibrosis Scientific Reports Oxidative stress Idiopathic pulmonary fibrosis Multi-omics Mendelian randomization analysis Colocalization analysis |
| title | Investigating the potential of oxidative stress-related gene as predictive markers in idiopathic pulmonary fibrosis |
| title_full | Investigating the potential of oxidative stress-related gene as predictive markers in idiopathic pulmonary fibrosis |
| title_fullStr | Investigating the potential of oxidative stress-related gene as predictive markers in idiopathic pulmonary fibrosis |
| title_full_unstemmed | Investigating the potential of oxidative stress-related gene as predictive markers in idiopathic pulmonary fibrosis |
| title_short | Investigating the potential of oxidative stress-related gene as predictive markers in idiopathic pulmonary fibrosis |
| title_sort | investigating the potential of oxidative stress related gene as predictive markers in idiopathic pulmonary fibrosis |
| topic | Oxidative stress Idiopathic pulmonary fibrosis Multi-omics Mendelian randomization analysis Colocalization analysis |
| url | https://doi.org/10.1038/s41598-025-02579-7 |
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