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 (FEV ₁) and FEV ₁/forced vital capacity (FEV ₁/FVC ), respectively. Weighted genetic risk scores (GRS s) for FEV ₁ and FEV ₁/FVC were constructed. At age 10, FEV ₁, FVC , FEV ₁/FVC , forced expiratory flow between 25% and 75% (FEF _25‐75), and forced expiratory flow at 75% (FEF ₇₅) of FVC were measured, and information on asthma was obtained by parental‐reported questionnaires. The FEV ₁‐GRS was associated with lower childhood FEV ₁, FEV ₁/FVC , and FEF ₇₅ (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 FEV ₁/FVC ‐GRS was associated with lower childhood FEV ₁/FVC and FEF ₇₅ (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 FEV ₁‐GRS with FEF _25‐75, FEV ₁, FEF ₇₅, and FVC , and of FEV ₁/FVC ‐GRS with FEV ₁/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.