Circulating proteomic landscape of lung function

Area of Science:

• Pulmonary Medicine
• Proteomics
• Genetics

Background:

• Genetic and epigenetic studies have identified genes related to lung function.
• Proteomics offers direct insights into pathophysiologic processes but remains underexplored in lung function research.

Purpose of the Study:

• To identify circulating proteins associated with lung function.
• To explore novel protein biomarkers for respiratory conditions.

Main Methods:

• Investigated spirometry parameters (FEV1, FVC, FEV1/FVC) in relation to 4693 circulating proteins across five cohorts (20,823 adults).
• Used robust linear regression adjusting for confounders and meta-analysis via inverse-variance weighting.
• Validated associations in the UK Biobank using the Olink 3K platform.

Main Results:

• 1055 proteins significantly associated with lung function traits (p<1×10^-5) in a multi-ancestry population.
• Enriched pathways involved inflammation and organismal injury; STAT3 and EGFR identified as potential orchestrators.
• 411 protein associations validated; 179 related to COPD; preliminary causal evidence for 34 proteins via Mendelian randomisation.
• 89% of associated proteins were novel in relation to lung function.

Conclusions:

• Identified novel protein-lung function associations.
• Findings may improve understanding of lung disease pathogenesis.
• Potential for discovery of circulating biomarkers and development of new management strategies for respiratory conditions.