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- Imboden, Medea, et al.
(författare)
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Epigenome-wide association study of lung function level and its change
- 2019
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Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 54:1
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Tidskriftsartikel (refereegranskat)abstract
- Previous reports link differential DNA methylation (DNAme) to environmental exposures that are associated with lung function. Direct evidence on lung function DNAme is, however, limited. We undertook an agnostic epigenome-wide association study (EWAS) on pre-bronchodilation lung function and its change in adults.In a discovery-replication EWAS design, DNAme in blood and spirometry were measured twice, 6-15 years apart, in the same participants of three adult population-based discovery cohorts (n=2043). Associated DNAme markers (p<5×10-7) were tested in seven replication cohorts (adult: n=3327; childhood: n=420). Technical bias-adjusted residuals of a regression of the normalised absolute β-values on control probe-derived principle components were regressed on level and change of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and their ratio (FEV1/FVC) in the covariate-adjusted discovery EWAS. Inverse-variance-weighted meta-analyses were performed on results from discovery and replication samples in all participants and never-smokers.EWAS signals were enriched for smoking-related DNAme. We replicated 57 lung function DNAme markers in adult, but not childhood samples, all previously associated with smoking. Markers not previously associated with smoking failed replication. cg05575921 (AHRR (aryl hydrocarbon receptor repressor)) showed the statistically most significant association with cross-sectional lung function (FEV1/FVC: pdiscovery=3.96×10-21 and pcombined=7.22×10-50). A score combining 10 DNAme markers previously reported to mediate the effect of smoking on lung function was associated with lung function (FEV1/FVC: p=2.65×10-20).Our results reveal that lung function-associated methylation signals in adults are predominantly smoking related, and possibly of clinical utility in identifying poor lung function and accelerated decline. Larger studies with more repeat time-points are needed to identify lung function DNAme in never-smokers and in children.
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| 2. |
- Lindgren, Anna, et al.
(författare)
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Individual whole-body concentration of (137)Cesium is associated with decreased blood counts in children in the Chernobyl-contaminated areas, Ukraine, 2008-2010.
- 2015
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Ingår i: Journal of Exposure Science & Environmental Epidemiology. - : Springer Science and Business Media LLC. - 1559-064X .- 1559-0631. ; 25:3, s. 334-342
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Tidskriftsartikel (refereegranskat)abstract
- The Narodichesky region, Zhitomir Oblast, Ukraine, is situated ∼80 km from the Chernobyl Nuclear Power Plant, which exploded in 1986 and polluted the environment. A previous study found that children living in villages with high activity of (137)Cesium (Cs) in the soil had decreased levels of hemoglobin, erythrocytes and thrombocytes. These findings motivated the present study that used a more comprehensive exposure assessment, including individual whole-body concentrations (WBC) of (137)Cs (Bq/kg). This cross-sectional sample examined between 2008-2010, included 590 children in the age 0-18 years. Children with higher individual log(WBC) activity in the body had significantly decreased hemoglobin, erythrocyte and thrombocyte counts. The effect of log(WBC) on decreased thrombocyte count was only seen in children older than 12 years. The average village activity of (137)Cs (kBq/m(2)) in soil was associated with decreased blood counts only indirectly, through (137)Cs in the body as an intermediate variable. Children in this study were born at least 4 years after the accident and thus exposed to low doses of ionizing radiation from (137)Cs. This cross-sectional study indicates that low levels may be associated with decreased blood counts, but we cannot exclude that these results are due to residual confounding factors.Journal of Exposure Science and Environmental Epidemiology advance online publication, 25 September 2013; doi:10.1038/jes.2013.60.
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| 3. |
- 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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