Polygenic COPD Risk Impairs Lung Growth Only in High-PM2.5 Swiss Children

The BILD birth cohort measured infant tidal breathing at one month and spirometry at age six while estimating residential PM2.5 and NO2 exposure and deriving a polygenic risk score validated in adult COPD GWAS. Growth trajectories diverged only above the 15.3 μg/m³ PM2.5 threshold, with high-risk children showing roughly 0.4 z-score lower FEV1 growth; similar interaction appeared for NO2 above 28.3 μg/m³. This gene-environment pattern suggests early-life pollution may lock in lower maximal lung function, a trajectory known to raise later COPD incidence independent of smoking.

Prior observational work in the same cohort and the larger SAPALDIA study already linked traffic-related pollutants to slower FEV1 growth, yet neither quantified polygenic moderation. The current analysis therefore extends those findings by showing that genetic liability amplifies pollution effects before clinical symptoms appear, an interaction missed by purely environmental or purely genetic models. Socioeconomic position, unmeasured indoor sources, and maternal smoking remain potential residual confounders that could inflate the apparent interaction.

Follow-up through adolescence will test whether deficits persist or widen and whether moving to cleaner areas attenuates trajectories. Policy modeling should incorporate childhood exposure ceilings below current EU limits if these early deficits prove irreversible.