Department of Epidemiology and Health Statistics, School of Public Health, Hangzhou Medical College, Hangzhou, China.
Department of Big Data in Health Science, School of Public Health, Zhejiang University School of Medicine, Hangzhou, China.
Thorax. 2024 Aug 19;79(9):878-882. doi: 10.1136/thorax-2024-221398.
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.
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可改变疾病进程的药物。在这里,我们整合了人类基因组学和蛋白质组学来研究 2769 种血浆蛋白与 IPF 之间的因果关联。我们的孟德尔随机分析确定了与 IPF 相关的 9 种蛋白质,其中 3 种(FUT3、ADAM15 和 USP28)存在共定位。ADAM15 是最有前途的候选蛋白,这一结论得到了血液和肺组织中表达数量性状基因座分析的支持。这些发现为 IPF 的发病机制提供了新的见解,并为应对这种毁灭性疾病的临床挑战提供了转化机会。