Genetic risk for adult obstructive lung function and its early life associations

Chronic obstructive pulmonary disease may partly originate in early life under influence from prenatal or early postnatal risk factors, including genetic predisposition.

We investigated the extent to which the genetic predisposition to adult obstructive lung function manifests already at birth and throughout childhood in terms of impaired lung function, bronchial responsiveness, and asthma-related symptoms.

We constructed a polygenic risk score (PRS) for adult obstructive lung function (FEV₁/forced vital capacity [FVC]) and associated it with neonatal and childhood lung function, bronchial responsiveness, asthma, and respiratory tract infections in the COPSAC (Copenhagen Prospective Studies on Asthma in Childhood) birth cohorts, and with hospitalization for wheeze, asthma, and infections in 114,283 unrelated individuals from the The Lundbeck Foundation Initiative for Integrative Psychiactric Research (iPSYCH) cohort.

The FEV₁/FVC PRS was associated with obstructive lung function shortly after birth (eg, neonatal FEV_0.5/FVC [β: -0.20; 95% CI: -0.31 to -0.09; P < .0003]), with continued progression into adolescence. A higher PRS was also linked to an increased risk of severe wheeze/asthma episodes (odds ratio: 1.24; 95% CI: 1.19-1.29; P = 1.6 × 10^-26) and lower respiratory tract infections (odds ratio: 1.09; 95% CI: 1.06-1.12; P = 3.5 × 10^-8) requiring hospitalization, which was evident a few months after birth. In COPSAC₂₀₀₀, there was no evidence of asthma exacerbations mediating the association between FEV₁/FVC PRS and lung function by age 18 years.

Genetic predisposition to obstructive lung function was evident shortly after birth in terms of impaired neonatal lung function and increased susceptibility to severe wheeze, asthma, and lower respiratory tract infections. This indicates prenatal life and early childhood as a window of opportunity for improving lung health in adulthood.