Background: The concept of the early origins of disease suggests that several mechanisms operate early in life, including the genetics of chronic obstructive pulmonary disease (COPD). Little is known about this influencing lung function across the lifespan.

Aims: (1) To calculate an individual polygenic risk score (PRS) using gene variants previously linked to COPD; (2) To evaluate its association with lung function from childhood to adulthood.

Methods: A PRS was calculated in subjects from 13 population-based studies included in Chronic Airway Diseases Early Stratification (CADSET) based on 82 genetic variants associated with COPD by the largest genome-wide association study to date (35,735 cases/222,076 controls) (Sakornsakolpat et al. Nat Genet 2019;51(3):494-505). The PRS was then tested for association with lung function at different ages using linear regressions. Results from each cohort were meta-analyzed by age groups: preschool age, school age, puberty, post-puberty, young adulthood, adulthood, late adulthood, and elderly.

Results: The association of the PRS with lung function was tested in 44,830 individuals (4-84 years). It was significantly associated with reduced FEV₁/FVC from school age (?: -0.14, 95%CI: -0.16,-0.12, p=9.12x10^-45) to elderly (?: -0.15, 95%CI: -0.17,-0.13, p=1.53x10^-50). Associations with reduced FEV₁ were also found albeit not consistently with FVC. There was no major effect modification by age, gender, or smoking.

Conclusions: We found strong associations between a PRS for adult COPD with lung function across ages, suggesting that a higher genetic risk for adult COPD might be linked to poor lung function already since childhood.