Genetic Risk for Adult Obstructive Lung Function and Its Early-Life Associations

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

OBJECTIVE: We investigated to which extent 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.

METHODS: We constructed a polygenic risk score (PRS) for adult obstructive lung function (FEV1/FVC) and associated it with neonatal and childhood lung function, bronchial responsiveness, asthma, and respiratory tract infections in the COPSAC birth cohorts, and with hospitalization for wheeze, asthma, and infections in 114,283 unrelated individuals from the IPSYCH cohort.

RESULTS: The FEV1/FVC PRS was associated with obstructive lung function shortly after birth (e.g., neonatal FEV0.5/FVC (β: -0.20 [-0.31;-0.09], P < 0.0003)), with continued progression into adolescence. A higher PRS was also linked to an increased risk of severe wheeze/asthma episodes (OR 1.24 [1.19;1.29], P = 1.6∙10-26) and lower respiratory tract infections (OR 1.09 [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.

CONCLUSION: 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.