基于基因的全蛋白质组扫描揭示了特发性肺纤维化的潜在致病血浆蛋白。

IF 9 1区医学 Q1 RESPIRATORY SYSTEM

Thorax Pub Date : 2024-08-19 DOI:10.1136/thorax-2024-221398

Jiahao Zhu, Houpu Liu, Rui Gao, Ruicheng Gong, Jing Wang, Dan Zhou, Min Yu, Yingjun Li

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引用次数: 0

摘要

特发性肺纤维化（IPF）是一种致命的肺部疾病，目前尚无可靠的生物标志物或疾病治疗药物。在这里，我们整合了人类基因组学和蛋白质组学，研究了 2769 种血浆蛋白与 IPF 之间的因果关系。我们的孟德尔随机分析确定了九种与 IPF 相关的蛋白质，其中三种（FUT3、ADAM15 和 USP28）是共定位的。在血液和肺组织中的表达定量性状位点分析支持下，ADAM15 成为最重要的候选蛋白。这些发现为了解 IPF 的病因提供了新的视角，并为应对这种毁灭性疾病的临床挑战提供了转化机会。

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Genetic-informed proteome-wide scan reveals potential causal plasma proteins for idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease for which there are no reliable biomarkers or disease-modifying drugs. Here, we integrated human genomics and proteomics to investigate the causal associations between 2769 plasma proteins and IPF. Our Mendelian randomisation analysis identified nine proteins associated with IPF, of which three (FUT3, ADAM15 and USP28) were colocalised. ADAM15 emerged as the top candidate, supported by expression quantitative trait locus analysis in both blood and lung tissue. These findings provide novel insights into the aetiology of IPF and offer translational opportunities in response to the clinical challenges of this devastating disease.

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来源期刊

Thorax 医学-呼吸系统

CiteScore

16.10

自引率

2.00%

发文量

197

审稿时长

1 months

期刊介绍： Thorax stands as one of the premier respiratory medicine journals globally, featuring clinical and experimental research articles spanning respiratory medicine, pediatrics, immunology, pharmacology, pathology, and surgery. The journal's mission is to publish noteworthy advancements in scientific understanding that are poised to influence clinical practice significantly. This encompasses articles delving into basic and translational mechanisms applicable to clinical material, covering areas such as cell and molecular biology, genetics, epidemiology, and immunology.