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Influence of genetic variants on childhood lung functionThe Generation R Study.

Research paper by Sara S Shagiwal, Herman T HT den Dekker, Johan C JC de Jongste, Guy G GG Brusselle, Vincent W V VWV Jaddoe, Janine F JF Felix, Liesbeth L Duijts

Indexed on: 09 Jun '18Published on: 09 Jun '18Published in: Pediatric Allergy and Immunology



Abstract

Genetic variants associated with adult lung function could already exert effects in 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 3,347 children, we selected 7 and 20 SNPs associated with adult forced expiratory volume in 1 second (FEV ) and FEV /forced vital capacity (FEV /FVC), respectively. Weighted genetic risk scores (GRSs) for FEV and FEV /FVC were constructed. At age 10 years, FEV , FVC, FEV /FVC, forced expiratory flow between 25-75% (FEF ) and at 75% (FEF ) of FVC were measured, and information on asthma was obtained by parental reported questionnaires. The FEV -GRS was associated with lower childhood FEV , FEV /FVC and FEF (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 /FVC-GRS was associated with lower childhood FEV /FVC and FEF (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 and FEV /FVC-GRSs with FEF , FEV , FEF , FVC and FEV /FVC and FEF , respectively, were stronger among children exposed to non-atopic mothers, smoking during pregnancy, in childhood or those born with a lower birthweight, respectively, (p-values for interaction < 0.05). GRSs were not associated with asthma. Adult lung function-related genetic variants were associated with childhood lung function. Maternal atopy, smoking during pregnancy, in childhood, and birthweight modified the observed effects. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.