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% (FEF_25-75 ), 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 FEF_25-75 , FEV₁ , FEF₇₅ , and FVC, and of FEV₁ /FVC-GRS with FEV₁ /FVC and FEF_25-75 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.