Influence of genetic variants on childhood lung function – The Generation R Study |
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| Authors: | Sara S. Shagiwal Herman T. den Dekker Johan C. de Jongste Guy G. Brusselle Vincent W. V. Jaddoe Janine F. Felix Liesbeth Duijts |
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| Affiliation: | 1. The Generation R Study Group, Division of Neonatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands;2. Department of Pediatrics, Division of Respiratory Medicine and Allergology, Division of Neonatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands;3. Department of Epidemiology, Division of Neonatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands;4. Department of Respiratory Medicine and Allergology, Division of Neonatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands;5. Department of Pediatrics, Division of Neonatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands |
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| Abstract: | 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. |
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| Keywords: | asthma child genetics lung function spirometry |
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