| 1. |
- Kupers, LK, et al.
(författare)
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Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1893-
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Tidskriftsartikel (refereegranskat)abstract
- Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10−7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10−74) and BMI in pregnancy (3/914, p = 1.13x10−3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.
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| 2. |
- Czamara, D, et al.
(författare)
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Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2548-
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.
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| 3. |
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| 4. |
- Sikdar, S, et al.
(författare)
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Comparison of smoking-related DNA methylation between newborns from prenatal exposure and adults from personal smoking
- 2019
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 11:13, s. 1487-1500
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Cigarette smoking influences DNA methylation genome wide, in newborns from pregnancy exposure and in adults from personal smoking. Whether a unique methylation signature exists for in utero exposure in newborns is unknown. Materials & methods: We separately meta-analyzed newborn blood DNA methylation (assessed using Illumina450k Beadchip), in relation to sustained maternal smoking during pregnancy (9 cohorts, 5648 newborns, 897 exposed) and adult blood methylation and personal smoking (16 cohorts, 15907 participants, 2433 current smokers). Results & conclusion: Comparing meta-analyses, we identified numerous signatures specific to newborns along with many shared between newborns and adults. Unique smoking-associated genes in newborns were enriched in xenobiotic metabolism pathways. Our findings may provide insights into specific health impacts of prenatal exposure on offspring.
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| 6. |
- Marinovich, ML, et al.
(författare)
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Developing evidence-based recommendations for optimal interpregnancy intervals in high-income countries: protocol for an international cohort study
- 2019
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 9:1, s. e027941-
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Tidskriftsartikel (refereegranskat)abstract
- Short interpregnancy interval (IPI) has been linked to adverse pregnancy outcomes. WHO recommends waiting at least 2 years after a live birth and 6 months after miscarriage or induced termination before conception of another pregnancy. The evidence underpinning these recommendations largely relies on data from low/middle-income countries. Furthermore, recent epidemiological investigations have suggested that these studies may overestimate the effects of IPI due to residual confounding. Future investigations of IPI effects in high-income countries drawing from large, population-based data sources are needed to inform IPI recommendations. We aim to assess the impact of IPIs on maternal and child health outcomes in high-income countries.Methods and analysisThis international longitudinal retrospective cohort study will include more than 18 million pregnancies, making it the largest study to investigate IPI in high-income countries. Population-based data from Australia, Finland, Norway and USA will be used. Birth records in each country will be used to identify consecutive pregnancies. Exact dates of birth and clinical best estimates of gestational length will be used to estimate IPI. Administrative birth and health data sources with >99% coverage in each country will be used to identify maternal sociodemographics, pregnancy complications, details of labour and delivery, birth and child health information. We will use matched and unmatched regression models to investigate the impact of IPI on maternal and infant outcomes, and conduct meta-analysis to pool results across countries.Ethics and disseminationEthics boards at participating sites approved this research (approval was not required in Finland). Findings will be published in peer-reviewed journals and presented at international conferences, and will inform recommendations for optimal IPI in high-income countries. Findings will provide important information for women and families planning future pregnancies and for clinicians providing prenatal care and giving guidance on family planning.
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