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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.

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

作者信息

Wang Yuhao, Zhang Zhao, Zhang Hongnan, Xu Luyao, Huang Shuling, Wen Ying, Zhuang Zhiming, Li Xiaoxin, Lu Jinyi, Li Xudong

机构信息

Guangdong Research Center of Occupational Hygiene, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou, 510399, Guangdong, China.

Guangzhou Center for Disease Control and Prevention (Guangzhou Health Supervision institute), Guangzhou, 510440, Guangdong, China.

出版信息

Sci Rep. 2025 Jul 1;15(1):21228. doi: 10.1038/s41598-025-02579-7.

本研究通过多组学数据整合，探究将氧化应激与特发性肺纤维化（IPF）联系起来的基因。我们从GeneCards收集了氧化应激相关基因，并整合了基因表达（eQTL）、DNA甲基化（mQTL）和蛋白质表达（pQTL）的数据。Allen等人关于IPF的全基因组关联研究（GWAS）数据用作发现集，FinnGen R10用于验证。基于汇总数据的孟德尔随机化（SMR）和共定位分析评估了相互作用和共享的因果变异，随后进行多组学整合及组织特异性验证。SMR和共定位筛选在发现队列中鉴定出90个与IPF相关的mQTL、15个eQTL和2个pQTL（KRT18和FOXO1）。在FinnGen队列中验证了12个mQTL，MUC1显示出强烈的SMR和共定位证据（eQTL）。多组学整合验证了NDUFA9（mQTL-eQTL）水平和FOXO1（mQTL-eQTL-pQTL）。我们的研究确定了IPF发病机制中关键的氧化应激相关基因（即FOXO1和NDUFA9），强调需要进一步研究以指导预防和治疗。