Pre-bronchodilator lung function including forced vital capacity (FVC), forced expiratory flow in 1 second (FEV 1 ), their ratio (FEV 1 /FVC), and forced expiratory flow 25–75% (FEF 25–75 ) measured at age 10, 18, and 26 years in the Isle of Wight birth cohort was analyzed for developmental patterns (trajectories). Early life risk factors before the age of 10 years were assessed for the trajectories. Method Members of the birth cohort (1989/90) were followed at age 1, 2, 4, 10, 18, and 26 years. Allergic sensitization and questionnaire data were collected. Spirometry tests were performed and evaluated according to the American Thoracic Society (ATS) criteria at 10, 18, and 26 years. To identify developmental trajectories for FVC, FEV 1 , FEV 1 /FVC, and FEF 25–75 from 10 to 26 years, a finite mixture model was applied to the longitudinal lung function data, separately for males and females. Associations of early life factors with the respective lung function trajectories were assessed using log-linear and logistic regression analyses. Results Both high and low lung function trajectories were observed in men and women. FVC continued to grow beyond 18 years in men and women, whereas FEV 1 peaked at age 18 years in female trajectories and in one male trajectory. For the FEV 1 /FVC ratios and FEF 25–75 most trajectories appeared highest at age 18 and declined thereafter. However, the low FEV 1 /FVC trajectory in both sexes showed an early decline at 10 years. Lower birth weight was linked with lower lung function trajectories in males and females. Eczema in the first year of life was a risk factor for later lung function deficits in females, whereas the occurrence of asthma at 4 years of age was a risk factor for later lung function deficits in males. A positive skin prick test at age four was a risk for the low FEV 1 trajectory in females and for the low FEV 1 /FVC trajectory in males. Conclusion Men and women showed distinctive lung function trajectories and associated risk factors. Lower lung function trajectories can be explained by not achieving maximally attainable function at age 18 years and by a function decline from 18 to 26 years. Electronic supplementary material The online version of this article (10.1186/s12931-019-1068-0) contains supplementary material, which is available to authorized users.

Background Breastfeeding is protective against many long-term diseases, yet the mechanisms involved are unknown. Leptin gene ( LEP ) is reported to be associated with body mass index (BMI). On the other hand, breastfeeding duration has been found to be associated with DNA methylation (DNAm) of the LEP gene. Therefore, epigenetic regulation of LEP may represent the mechanism underlying the protective effect of breastfeeding duration against obesity. Methods In the Isle of Wight Birth Cohort, peripheral blood DNAm at 23 cytosine-phosphate-guanine sites (CpGs) in the LEP locus in 10-year-old ( n = 297) samples and 16 CpGs in 18-year-old ( n = 305) samples, were generated using the Illumina Infinium MethylationEPIC and HumanMethylation450 Beadchips respectively and tested for association with breastfeeding duration (total and exclusive) using linear regression. To explore the association between breastfeeding durations and genome-wide DNAm, epigenome-wide association studies (EWASs) and differential methylation region (DMR) analyses were performed. BMI trajectories spanning the first 18 years of life were used as the outcome to test the association with breastfeeding duration (exposure) using multi-nominal logistic regression. Mediation analysis was performed for significant CpG sites. Results Both total and exclusive breastfeeding duration were associated with DNAm at four LEP CpG sites at 10 years ( P value < 0.05), and not at 18 years. Though no association was observed between breastfeeding duration and genome-wide DNAm, DMR analyses identified five significant differentially methylated regions (Sidak adjusted P value < 0.05). Breastfeeding duration was also associated with the early transient overweight trajectory. Furthermore, DNAm of LEP was associated with this trajectory at one CpG site and early persistent obesity at another, though mediation analysis was not significant. Conclusions Breastfeeding duration is associated with LEP methylation at age 10 years and BMI trajectory. LEP DNAm is also significantly associated with BMI trajectories throughout childhood, though sample sizes were small. However, mediation analysis did not demonstrate that DNAm of LEP explained the protective effect of breastfeeding against childhood obesity. Electronic supplementary material The online version of this article (10.1186/s13148-019-0727-9) contains supplementary material, which is available to authorized users.

There is emerging evidence on DNA methylation (DNAm) variability over time; however, little is known about dynamics of DNAm patterns during pregnancy. We performed an epigenome-wide longitudinal DNAm study of a well-characterized sample of young women from the Swedish Born into Life study, with repeated blood sampling before, during and after pregnancy (n = 21), using the Illumina Infinium MethylationEPIC array. We conducted a replication in the Isle of Wight third-generation birth cohort (n = 27), using the Infinium HumanMethylation450k BeadChip. We identified 196 CpG sites displaying intra-individual longitudinal change in DNAm with a false discovery rate (FDR) P < .05. Most of these (91%) showed a decrease in average methylation levels over the studied period. We observed several genes represented by ⩾3 differentially methylated CpGs: HOXB3, AVP, LOC100996291, and MicroRNA 10a. Of 36 CpGs available in the replication cohort, 17 were replicated, all but 2 with the same direction of association (replication P < .05). Biological pathway analysis demonstrated that FDR-significant CpGs belong to genes overrepresented in metabolism-related pathways, such as adipose tissue development, regulation of insulin receptor signaling, and mammary gland fat development. These results contribute to a better understanding of the biological mechanisms underlying important physiological alterations and adaptations for pregnancy and lactation.

No abstract

Little is known about whether DNA methylation (DNAm) of cytosine-phosphate-guanine (CpG) sites at birth predicts patterns of lung function development. We used heel prick DNAm from the F1-generation of Isle of Wight birth cohort (IOWBC-F1) for discovery of CpGs associated with lung function trajectories (Forced Expiratory Volume, Forced Vital Capacity, their ratio, and Forced Expiratory Flow at 25–75%) over the first 26 years, stratified by sex. We replicated the findings in the Avon Longitudinal Study of Parents and Children (ALSPAC) using cord blood DNAm.Epigenome-wide screening was applied to identify CpGs associated with lung function trajectories in 396 boys, and 390 girls of IOWBC-F1. Replication in ALSPAC focused on lung function at ages 8, 15 and 24 years. Statistically significantly replicated CpGs were investigated for consistency in direction of association between cohorts, stability of DNAm over time in IOWBC-F1, relevant biological processes, and for association with gene expression (n=161) in IOWBC F2-generation (IOWBC-F2).Differential DNAm of 8 CpGs on genes GLUL, MYCN, HLX, LHX1, COBL, COL18A1, STRA6, and WNT11 involved in developmental processes, were significantly associated with lung function in the same direction in IOWBC-F1 and ALSPAC, and showed stable patterns at birth, age 10 and 18 years between high and low lung function trajectories in IOWBC-F1. CpGs on LHX1 and COL18A1 were linked to gene expression in IOWBC-F2.In two large cohorts, novel DNAm at birth were associated with patterns of lung function in adolescence and early adulthood providing possible targets for preventative interventions against adverse pulmonary function development.