Influence of genetic variants on childhood lung function - The Generation R Study

Genetic variants associated with adult lung function could already exert the effects on childhood lung function. We aimed to examine the associations of adult lung function-related genetic variants with childhood lung function and asthma, and whether these associations were modified by atopic predisposition, tobacco smoke exposure, or early growth characteristics. In a population-based prospective cohort study among 3347 children, we selected 7 and 20 single nucleotide polymorphisms (SNPs) associated with adult forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FEV1/FVC), respectively. Weighted genetic risk scores (GRSs) for FEV1 and FEV1/FVC were constructed. At age 10, FEV1, FVC, FEV1/FVC, forced expiratory flow between 25% and 75% (FEF25-75), and forced expiratory flow at 75% (FEF75) of FVC were measured, and information on asthma was obtained by parental-reported questionnaires. The FEV1-GRS was associated with lower childhood FEV1, FEV1/FVC, and FEF75 (Z-score (95% CI): -0.03 (-0.05, -0.01), -0.03 (-0.05, -0.01), and -0.04 (-0.05, -0.01), respectively, per additional risk allele). The FEV1/FVC-GRS was associated with lower childhood FEV1/FVC and FEF75 (Z-score (95% CI): -0.04 (-0.05, -0.03) and -0.03 (-0.05, -0.02), respectively, per additional risk allele). Effect estimates of FEV1-GRS with FEF25-75, FEV1, FEF75, and FVC, and of FEV1/FVC-GRS with FEV1/FVC and FEF25-75 were stronger among children exposed to non-atopic mothers, smoking during pregnancy or in childhood, or those born with a lower birthweight, respectively (P-values for interaction < .05). Genetic risk scores were not associated with asthma. Adult lung function-related genetic variants were associated with childhood lung function. Maternal atopy, smoking during pregnancy or in childhood, and birthweight modified the observed effects.