Dataset Information

Consistency and Variability of DNA Methylation in Women During Puberty, Young Adulthood, and Pregnancy.

ABSTRACT: Prior DNA methylation (DNA-m) analyses have identified cytosine-phosphate-guanine (CpG) sites, which show either a significant change or consistency during lifetime. However, the proportion of CpGs that are neither significantly different nor consistent over time (indifferent CpGs) is unknown. We investigated the methylation dynamics, both longitudinal changes and consistency, in women from preadolescence to late pregnancy using DNA-m of peripheral blood cells. Consistency of cell type-adjusted DNA-m between paired individuals was assessed by regressing CpGs of subsequent age on the prior, stability by intraclass correlation coefficients (>0.5), and changes by linear mixed models. In the first 2 transitions (10-18?years and 18?years to early pregnancy), 19.5% and 20.9% CpGs were consistent, but only 0.35% in the third transition (from early to late pregnancy). Significant changes in methylation were found in 0.7%, 5.6%, and 0% CpGs, respectively. Functional enrichment analyses of genes with significant changes in DNA-m in early pregnancy (5.6%) showed that the maternal DNA-m seems to reflect signaling pathways between the uterus and the trophoblast. The transition from early to late pregnancy showed low consistency/stability and no changes, suggesting the presence of a large proportion of indifferent CpGs in late pregnancy.

SUBMITTER: Chen S

PROVIDER: S-EPMC5536379 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Consistency and Variability of DNA Methylation in Women During Puberty, Young Adulthood, and Pregnancy.

Chen Su S Mukherjee Nandini N Janjanam Vimala Devi VD Arshad S Hasan SH Kurukulaaratchy Ramesh J RJ Holloway John W JW Zhang Hongmei H Karmaus Wilfried W

Genetics & epigenetics 20170728

Prior DNA methylation (DNA-m) analyses have identified cytosine-phosphate-guanine (CpG) sites, which show either a significant change or consistency during lifetime. However, the proportion of CpGs that are neither significantly different nor consistent over time (indifferent CpGs) is unknown. We investigated the methylation dynamics, both longitudinal changes and consistency, in women from preadolescence to late pregnancy using DNA-m of peripheral blood cells. Consistency of cell type-adjusted ...[more]

PMID: 28811741

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Project description:ImportanceDNA methylation has been proposed as an epigenetic mechanism by which the childhood neighborhood environment may have implications for the genome that compromise adult health.ObjectiveTo ascertain whether childhood neighborhood socioeconomic disadvantage is associated with differences in DNA methylation by age 18 years.Design, setting, and participantsThis longitudinal cohort study analyzed data from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative birth cohort of children born between 1994 and 1995 in England and Wales and followed up from age 5 to 18 years. Data analysis was performed from March 15, 2019, to June 30, 2019.ExposuresHigh-resolution neighborhood data (indexing deprivation, dilapidation, disconnection, and dangerousness) collected across childhood.Main outcomes and measuresDNA methylation in whole blood was drawn at age 18 years. Associations between neighborhood socioeconomic disadvantage and methylation were tested using 3 prespecified approaches: (1) testing probes annotated to candidate genes involved in biological responses to growing up in socioeconomically disadvantaged neighborhoods and investigated in previous epigenetic research (stress reactivity-related and inflammation-related genes), (2) polyepigenetic scores indexing differential methylation in phenotypes associated with growing up in disadvantaged neighborhoods (obesity, inflammation, and smoking), and (3) a theory-free epigenome-wide association study.ResultsA total of 1619 participants (806 female individuals [50%]) had complete neighborhood and DNA methylation data. Children raised in socioeconomically disadvantaged neighborhoods exhibited differential DNA methylation in genes involved in inflammation (β = 0.12; 95% CI, 0.06-0.19; P < .001) and smoking (β = 0.18; 95% CI, 0.11-0.25; P < .001) but not obesity (β = 0.05; 95% CI, -0.01 to 0.11; P = .12). An epigenome-wide association study identified multiple CpG sites at an arraywide significance level of P < 1.16 × 10-7 in genes involved in the metabolism of hydrocarbons. Associations between neighborhood disadvantage and methylation were small but robust to family-level socioeconomic factors and to individual-level tobacco smoking.Conclusions and relevanceChildren raised in more socioeconomically disadvantaged neighborhoods appeared to enter young adulthood epigenetically distinct from their less disadvantaged peers. This finding suggests that epigenetic regulation may be a mechanism by which the childhood neighborhood environment alters adult health.

Dataset Information

Consistency and Variability of DNA Methylation in Women During Puberty, Young Adulthood, and Pregnancy.

Publications

Consistency and Variability of DNA Methylation in Women During Puberty, Young Adulthood, and Pregnancy.

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