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

Abstract

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.