Identifying potential drug targets for idiopathic pulmonary fibrosis: a mendelian randomization study based on the druggable genes

特发性肺纤维化 孟德尔随机化 可药性 医学 表达数量性状基因座 全基因组关联研究 基因 肿瘤科 生物 内科学 遗传学 单核苷酸多态性 基因型 遗传变异
作者
Zetao Liu,Zhiyu Peng,Huahang Lin,Ke Zhou,Linchuan Liang,Jie Cao,Zhaokang Huang,Jiandong Mei
出处
期刊:Respiratory Research [BioMed Central]
卷期号:25 (1) 被引量:1
标识
DOI:10.1186/s12931-024-02848-5
摘要

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic interstitial lung disease characterized by progressive dyspnea and decreased lung function, yet its exact etiology remains unclear. It is of great significance to discover new drug targets for IPF. Methods We obtained the cis-expression quantitative trait locus (cis-eQTL) of druggable genes from eQTLGen Consortium as exposure and the genome wide association study (GWAS) of IPF from the International IPF Genetics Consortium as outcomes to simulate the effects of drugs on IPF by employing mendelian randomization analysis. Then colocalization analysis was performed to calculate the probability of both cis-eQTL of druggable genes and IPF sharing a causal variant. For further validation, we conducted protein quantitative trait locus (pQTL) analysis to reaffirm our findings. Results The expression of 45 druggable genes was significantly associated with IPF susceptibility at FDR < 0.05. The expression of 23 and 15 druggable genes was significantly associated with decreased forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLco) in IPF patients, respectively. IPF susceptibility and two significant genes ( IL-7 and ABCB2 ) were likely to share a causal variant. The results of the pQTL analysis demonstrated that high levels of IL-7 in plasma are associated with a reduced risk of IPF (OR = 0.67, 95%CI: 0.47–0.97). Conclusion IL-7 stands out as the most promising potential drug target to mitigate the risk of IPF. Our study not only sheds light on potential drug targets but also provides a direction for future drug development in IPF.
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