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Early gestation as the critical time-window for changes in the prenatal environment to affect the adult human blood methylome.

Tobi EW, Slieker RC, Stein AD, Suchiman HE, Slagboom PE, van Zwet EW, Heijmans BT, Lumey LH - Int J Epidemiol (2015)

Bottom Line: The manipulation of pregnancy diets in animals can lead to changes in DNA methylation with phenotypic consequences in the offspring.Famine exposure during gestation weeks 1-10, but not weeks 11-20, 21-30 or 31-delivery, was associated with an increase in DNA methylation of CpG dinucleotides cg20823026 (FAM150B), cg10354880 (SLC38A2) and cg27370573 (PPAP2C) and a decrease of cg11496778 (OSBPL5/MRGPRG) (P < 5.9 × 10(-7), PFDR < 0.031).These changes represent a shift of 0.3-0.6 standard deviations and are linked to genes involved in growth, development and metabolism.

View Article: PubMed Central - PubMed

Affiliation: Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.

No MeSH data available.


Related in: MedlinePlus

QQ-plots of prenatal famine exposure during specific 10-week periods. Plots depicting the Observed statistic (y-axis) with the statistic as expected by chance given the number of tests (x-axis). The 95% confidence interval of this relationship is given by the grey area around the expected line (black) for the instance that the observed statistic exactly follows the expected statistic. Each dot is the test statistic for one CpG dinucleotide. Enrichments for associations that go beyond that expected by chance can be seen as deviations upward from the expected line and 95% CI area. The P-values were corrected for the inflation factor [weeks 1–10 (λ = 1.12), weeks 11–20 (λ = 1.12), weeks 21–30 (λ = 1.12), weeks 31-delivery (λ = 1.20)] and uncorrected QQ-plots are shown in Supplementary Figure 8, available as Supplementary data at IJE online.
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dyv043-F1: QQ-plots of prenatal famine exposure during specific 10-week periods. Plots depicting the Observed statistic (y-axis) with the statistic as expected by chance given the number of tests (x-axis). The 95% confidence interval of this relationship is given by the grey area around the expected line (black) for the instance that the observed statistic exactly follows the expected statistic. Each dot is the test statistic for one CpG dinucleotide. Enrichments for associations that go beyond that expected by chance can be seen as deviations upward from the expected line and 95% CI area. The P-values were corrected for the inflation factor [weeks 1–10 (λ = 1.12), weeks 11–20 (λ = 1.12), weeks 21–30 (λ = 1.12), weeks 31-delivery (λ = 1.20)] and uncorrected QQ-plots are shown in Supplementary Figure 8, available as Supplementary data at IJE online.

Mentions: We performed a separate EWAS of famine exposure during each of the four 10-week gestation periods. Quantile-Quantile plots (QQ-plots) representing the observed vs the expected test statistic for each evaluated CpG nucleotide given the number of performed tests are shown in Figure 1. For several CpGs, nominal P-values were lower than the expected distribution of P-values for famine exposure in weeks 1–10 of gestation. In contrast, no evidence for an association between DNA methylation and famine exposure in weeks 11–20, 21–30 or 31 to delivery was observed.


Early gestation as the critical time-window for changes in the prenatal environment to affect the adult human blood methylome.

Tobi EW, Slieker RC, Stein AD, Suchiman HE, Slagboom PE, van Zwet EW, Heijmans BT, Lumey LH - Int J Epidemiol (2015)

QQ-plots of prenatal famine exposure during specific 10-week periods. Plots depicting the Observed statistic (y-axis) with the statistic as expected by chance given the number of tests (x-axis). The 95% confidence interval of this relationship is given by the grey area around the expected line (black) for the instance that the observed statistic exactly follows the expected statistic. Each dot is the test statistic for one CpG dinucleotide. Enrichments for associations that go beyond that expected by chance can be seen as deviations upward from the expected line and 95% CI area. The P-values were corrected for the inflation factor [weeks 1–10 (λ = 1.12), weeks 11–20 (λ = 1.12), weeks 21–30 (λ = 1.12), weeks 31-delivery (λ = 1.20)] and uncorrected QQ-plots are shown in Supplementary Figure 8, available as Supplementary data at IJE online.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588866&req=5

dyv043-F1: QQ-plots of prenatal famine exposure during specific 10-week periods. Plots depicting the Observed statistic (y-axis) with the statistic as expected by chance given the number of tests (x-axis). The 95% confidence interval of this relationship is given by the grey area around the expected line (black) for the instance that the observed statistic exactly follows the expected statistic. Each dot is the test statistic for one CpG dinucleotide. Enrichments for associations that go beyond that expected by chance can be seen as deviations upward from the expected line and 95% CI area. The P-values were corrected for the inflation factor [weeks 1–10 (λ = 1.12), weeks 11–20 (λ = 1.12), weeks 21–30 (λ = 1.12), weeks 31-delivery (λ = 1.20)] and uncorrected QQ-plots are shown in Supplementary Figure 8, available as Supplementary data at IJE online.
Mentions: We performed a separate EWAS of famine exposure during each of the four 10-week gestation periods. Quantile-Quantile plots (QQ-plots) representing the observed vs the expected test statistic for each evaluated CpG nucleotide given the number of performed tests are shown in Figure 1. For several CpGs, nominal P-values were lower than the expected distribution of P-values for famine exposure in weeks 1–10 of gestation. In contrast, no evidence for an association between DNA methylation and famine exposure in weeks 11–20, 21–30 or 31 to delivery was observed.

Bottom Line: The manipulation of pregnancy diets in animals can lead to changes in DNA methylation with phenotypic consequences in the offspring.Famine exposure during gestation weeks 1-10, but not weeks 11-20, 21-30 or 31-delivery, was associated with an increase in DNA methylation of CpG dinucleotides cg20823026 (FAM150B), cg10354880 (SLC38A2) and cg27370573 (PPAP2C) and a decrease of cg11496778 (OSBPL5/MRGPRG) (P < 5.9 × 10(-7), PFDR < 0.031).These changes represent a shift of 0.3-0.6 standard deviations and are linked to genes involved in growth, development and metabolism.

View Article: PubMed Central - PubMed

Affiliation: Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.

No MeSH data available.


Related in: MedlinePlus