Influence of genetic variants on childhood lung function – The Generation R Study. Issue 6 (10th July 2018)

• Record Type: Journal Article
• Authors: Shagiwal, Sara S.; den Dekker, Herman T.; de Jongste, Johan C.; Brusselle, Guy G.; Jaddoe, Vincent W. V.; Felix, Janine F.; Duijts, Liesbeth
• Is Part Of: Pediatric allergy and immunology. Volume 29:Issue 6(2018)
• Page Start: 589
• Page End: 595
• Publication Date: 2018-07-10
• Subjects: asthma -- child -- genetics -- lung function -- spirometry; Allergy in children -- Periodicals; Immunologic diseases in children -- Periodicals; 617
• DOI: 10.1111/pai.12931
• Languages: English
• ISSNs: 0905-6157

Abstract

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 (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. Abstract :