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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 any prenatal famine exposure. 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 (λ = 1.14).
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dyv043-F3: QQ-plots of any prenatal famine exposure. 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 (λ = 1.14).

Mentions: Next we performed an EWAS of famine exposure in any of the gestation periods. A QQ-plot representing the observed vs the expected test statistic given the number of performed tests for each evaluated CpG nucleotide is shown in Figure 3. Methylation differences were seen for the CpG dinucleotides cg15659713 and cg26199857 (PFDR = 0.034, Figure 4). The estimates did not change after additional adjustment for smoking, current dietary characteristics or SES. There was no interaction between famine exposure and sex. The estimates were not affected by cell composition (Supplementary Table 4, available as Supplementary data at IJE online). Neither of these two CpG dinucleotides was associated with famine exposure limited to weeks 1–10, 11–20, 21–30 or weeks 31 to delivery, and the direction and the magnitude in each of these four exposure periods were similar to the estimate for the aggregate (Table 3). We further considered whether DNA methylation of these two CpG dinucleotides was dependent on the number of weeks of famine exposure. No relation between the number of weeks of famine exposure and DNA methylation of cg15659713 and cg26199857 was found in the individuals with any exposure to famine.Figure 3.


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 any prenatal famine exposure. 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 (λ = 1.14).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

dyv043-F3: QQ-plots of any prenatal famine exposure. 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 (λ = 1.14).
Mentions: Next we performed an EWAS of famine exposure in any of the gestation periods. A QQ-plot representing the observed vs the expected test statistic given the number of performed tests for each evaluated CpG nucleotide is shown in Figure 3. Methylation differences were seen for the CpG dinucleotides cg15659713 and cg26199857 (PFDR = 0.034, Figure 4). The estimates did not change after additional adjustment for smoking, current dietary characteristics or SES. There was no interaction between famine exposure and sex. The estimates were not affected by cell composition (Supplementary Table 4, available as Supplementary data at IJE online). Neither of these two CpG dinucleotides was associated with famine exposure limited to weeks 1–10, 11–20, 21–30 or weeks 31 to delivery, and the direction and the magnitude in each of these four exposure periods were similar to the estimate for the aggregate (Table 3). We further considered whether DNA methylation of these two CpG dinucleotides was dependent on the number of weeks of famine exposure. No relation between the number of weeks of famine exposure and DNA methylation of cg15659713 and cg26199857 was found in the individuals with any exposure to famine.Figure 3.

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