Influence of genetic variants on childhood lung function – The Generation R Study

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 ) and FEV /forced vital capacity (FEV /FVC), respectively. Weighted genetic risk scores (GRSs) for FEV and FEV /FVC were constructed. At age 10, FEV , FVC, FEV /FVC, forced expiratory flow between 25% and 75% (FEF ), and forced expiratory flow 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 -GRS with FEF , FEV , FEF , and FVC, and of FEV /FVC-GRS with FEV /FVC and FEF 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.

Antibiotic use favors early‐life allergies, intrauterine blood flow may influence respiratory allergies, and features of hyper‐IgE syndrome

“…The study population was recruited from the Generation R study, a Dutch prospective birth cohort. Findings from this cohort have been reported earlier in PAI . Here, information on early‐life wheeze was obtained from questionnaires, and children had pulmonary function tests performed between 8 and 12 years of age.…”

“…Findings from this cohort have been reported earlier in PAI. [12][13][14][15] Here, information on early-life wheeze was obtained from questionnaires, and children had pulmonary function tests performed between 8 and 12 years of age. Although results showed a relationship between a higher umbilical artery pulsatility index (PI) and umbilical artery PI/cerebral artery PI ratio, indicating fetal blood flow redistribution at the expense of the trunk, with more early wheezing, this association was not statistically significant.…”

Highlights and recent developments in airway diseases in EAACI journals (2018)

“…Preliminary results suggest that the polymorphism variant rs9325071 led to increased skin permeability as measured by transepidermal water loss. There is recent evidence suggesting that genetic variants related to adult lung function are associated with lung function and asthma in 10‐year‐old children . Other factors also played a role, such as maternal atopy, tobacco smoke exposure, and birth weight.…”

“…There is recent evidence suggesting that genetic variants related to adult lung function are associated with lung function and asthma in 10-year-old children. 30 Other factors also played a role, such as maternal atopy, tobacco smoke exposure, and birth weight.…”

Asthma from infancy to childhood, and allergy perception in adolescents

“…Various studies have recently been published in this journal concerning genetics and asthma. Similarly to this article, Shagiwal et al have examined the relationship between genetics and lung functions. The link between genetic variants, early wheeze, and viral infections has also been studied .…”