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- Merid, Simon Kebede, et al.
(författare)
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Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
- 2020
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Ingår i: Genome Medicine. - Stockholm : Karolinska Institutet, Dept of Clinical Science and Education, Södersjukhuset. - 1756-994X.
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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.
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- Nagrani, Rajini, et al.
(författare)
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Association of urinary and ambient black carbon, and other ambient air pollutants with risk of prediabetes and metabolic syndrome in children and adolescents.
- 2023
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Ingår i: Environmental pollution (Barking, Essex : 1987). - : Elsevier BV. - 1873-6424 .- 0269-7491. ; 317
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Tidskriftsartikel (refereegranskat)abstract
- The effects of exposure to black carbon (BC) on various diseases remains unclear, one reason being potential exposure misclassification following modelling of ambient air pollution levels. Urinary BC particles may be a more precise measure to analyze the health effects of BC. We aimed to assess the risk of prediabetes and metabolic syndrome (MetS) in relation to urinary BC particles and ambient BC and to compare their associations in 5453 children from IDEFICS/I. Family cohort. We determined the amount of BC particles in urine using label-free white-light generation under femtosecond pulsed laser illumination. We assessed annual exposure to ambient air pollutants (BC, PM2.5 and NO2) at the place of residence using land use regression models for Europe, and we calculated the residential distance to major roads (≤250m vs. more). We analyzed the cross-sectional relationships between urinary BC and air pollutants (BC, PM2.5 and NO2) and distance to roads, and the associations of all these variables to the risk of prediabetes and MetS, using logistic and linear regression models. Though we did not observe associations between urinary and ambient BC in overall analysis, we observed a positive association between urinary and ambient BC levels in boys and in children living ≤250m to a major road compared to those living >250m away from a major road. We observed a positive association between log-transformed urinary BC particles and MetS (ORper unit increase=1.72, 95% CI=1.21; 2.45). An association between ambient BC and MetS was only observed in children living closer to a major road. Our findings suggest that exposure to BC (ambient and biomarker) may contribute to the risk of MetS in children. By measuring the internal dose, the BC particles in urine may have additionally captured non-residential sources and reduced exposure misclassification. Larger studies, with longitudinal design including measurement of urinary BC at multiple time-points are warranted to confirm our findings.
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