| 1. |
- Kirkeleit, Jorunn, et al.
(författare)
-
Early life origins of lung ageing : A study of lung function decline the ECRHS and NFBC1966 cohorts
- 2020
-
Ingår i: European Respiratory Journal. - : ERS Publications. - 0903-1936 .- 1399-3003. ; 56
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objective: To determine whether early life factors associated with poor lung growth and submaximal attained lung function contribute to accelerated lung function decline later in life.Methods: Participants in the European Community Respiratory Health Survey (ECRHS) and the Northern Finland Birth Cohort 1966 (NFBC1966) with lung function measured in a first (n=10,971), second (n=7,981) and third wave (n=4,849), aged 20 – 68 years, were included. Mean annual decline in maximum forced expired volume in 1 second (FEV1) and forced vital capacity (FVC) were main outcomes. Information on early life factors was provided by standardized interviews and questionnaires. We estimated the effect of early life factors including maternal age, parental smoking, season of birth, parental asthma and respiratory infections using mixed effects models, adjusted for age, FEV1 and FVC at baseline, height, and smoking habits.Results: Decline in FEV1 was accelerated in women born of a mother with asthma (β = 2.4 ml; 95% CI 0.6-4.3) or who smoked during pregnancy (1.9; 0.2-3.6), and in men having a father with asthma (3.5; 0.2-6.9) or born by Cesarean section (7.9; 1.6-14.2). Accelerated decline in FVC was associated with paternal asthma in men (4.3; 0.1-8.5) and early menarche (<12 years) in women (2.4; 0.4-4.4). No statistically significant effect on lung function decline was found for other investigated early life factors.Conclusion: Early life risk factors contribute to an accelerated lung function decline with ageing, following sex-specific patterns. Decline in FEV1 versus FVC showed slightly different patterns.
|
|
| 2. |
- Merid, Simon Kebede, et al.
(författare)
-
Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
- 2020
-
Ingår i: Genome Medicine. - Stockholm : Karolinska Institutet, Dept of Clinical Science and Education, Södersjukhuset. - 1756-994X.
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
|
|
