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Maternal pre-pregnancy BMI and gestational weight gain, offspring DNA methylation and later offspring adiposity: findings from the Avon Longitudinal Study of Parents and Children.

Sharp GC, Lawlor DA, Richmond RC, Fraser A, Simpkin A, Suderman M, Shihab HA, Lyttleton O, McArdle W, Ring SM, Gaunt TR, Davey Smith G, Relton CL - Int J Epidemiol (2015)

Bottom Line: There were no consistent associations of gestational weight gain with offspring DNA methylation.Our data suggest that both maternal obesity and, to a larger degree, underweight affect the neonatal epigenome via an intrauterine mechanism, but weight gain during pregnancy has little effect.We found some evidence that associations of maternal underweight with lower offspring adiposity and maternal obesity with greater offspring adiposity may be mediated via increased DNA methylation.

View Article: PubMed Central - PubMed

Affiliation: MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK, School of Social and Community Medicine, University of Bristol, Bristol, UK and gemma.sharp@bristol.ac.uk.

No MeSH data available.


Related in: MedlinePlus

Methylation (%) over time for offspring of obese (short dashed (green) line in a) or underweight (short dashed (green) line in b) mothers compared with offspring of normal weight mothers (long dashed (black) line). Ribbons indicate 95% confidence intervals.
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dyv042-F4: Methylation (%) over time for offspring of obese (short dashed (green) line in a) or underweight (short dashed (green) line in b) mothers compared with offspring of normal weight mothers (long dashed (black) line). Ribbons indicate 95% confidence intervals.

Mentions: Explicit longitudinal modelling of methylation at sites identified in cord blood as being associated with maternal obesity or underweight showed that this lack of overlap in EWAS hits between time points is likely due to postnatal resolution of differential methylation. Full results of this longitudinal analysis are presented in File S2 (available as Supplementary data at IJE online). Table 3 and Figure 4a show results of longitudinal analysis of the top five sites found differentially methylated in cord blood, between offspring of normal weight and obese mothers. At these sites, changes in methylation were stronger in early/mid childhood (age 0 to 7 years) than in late childhood/adolescence (age 7 to 17 years). Differences in methylation change were found at three of the top five sites. For example, at cg03270036 (on a CpG island shore at FAM129B), the estimated cord blood methylation in offspring of obese mothers was 8.9% lower than in offspring of normal weight mothers. During early/mid childhood, methylation decreased in the offspring of normal weight mothers but increased in the offspring of obese mothers (P-value for difference in changes during childhood 4 × 10−9), i.e. methylation differences here were being resolved during early childhood. During late childhood/adolescence however, offspring from both BMI groups had decreasing methylation, with no difference in rate of change. The effect of cellular heterogeneity from cord to peripheral blood is strong at cg00526953 (on a CpG island shore at an uncharacterized locus on chromosome 16): in Figure 4a, methylation increases during childhood for offspring of both BMI groups, whereas in Table 3 methylation decreases with age. This suggests that changing cell-type proportions are associated with increasing methylation, and after controlling for this, methylation decreases with age on average.Figure 4.


Maternal pre-pregnancy BMI and gestational weight gain, offspring DNA methylation and later offspring adiposity: findings from the Avon Longitudinal Study of Parents and Children.

Sharp GC, Lawlor DA, Richmond RC, Fraser A, Simpkin A, Suderman M, Shihab HA, Lyttleton O, McArdle W, Ring SM, Gaunt TR, Davey Smith G, Relton CL - Int J Epidemiol (2015)

Methylation (%) over time for offspring of obese (short dashed (green) line in a) or underweight (short dashed (green) line in b) mothers compared with offspring of normal weight mothers (long dashed (black) line). Ribbons indicate 95% confidence intervals.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588865&req=5

dyv042-F4: Methylation (%) over time for offspring of obese (short dashed (green) line in a) or underweight (short dashed (green) line in b) mothers compared with offspring of normal weight mothers (long dashed (black) line). Ribbons indicate 95% confidence intervals.
Mentions: Explicit longitudinal modelling of methylation at sites identified in cord blood as being associated with maternal obesity or underweight showed that this lack of overlap in EWAS hits between time points is likely due to postnatal resolution of differential methylation. Full results of this longitudinal analysis are presented in File S2 (available as Supplementary data at IJE online). Table 3 and Figure 4a show results of longitudinal analysis of the top five sites found differentially methylated in cord blood, between offspring of normal weight and obese mothers. At these sites, changes in methylation were stronger in early/mid childhood (age 0 to 7 years) than in late childhood/adolescence (age 7 to 17 years). Differences in methylation change were found at three of the top five sites. For example, at cg03270036 (on a CpG island shore at FAM129B), the estimated cord blood methylation in offspring of obese mothers was 8.9% lower than in offspring of normal weight mothers. During early/mid childhood, methylation decreased in the offspring of normal weight mothers but increased in the offspring of obese mothers (P-value for difference in changes during childhood 4 × 10−9), i.e. methylation differences here were being resolved during early childhood. During late childhood/adolescence however, offspring from both BMI groups had decreasing methylation, with no difference in rate of change. The effect of cellular heterogeneity from cord to peripheral blood is strong at cg00526953 (on a CpG island shore at an uncharacterized locus on chromosome 16): in Figure 4a, methylation increases during childhood for offspring of both BMI groups, whereas in Table 3 methylation decreases with age. This suggests that changing cell-type proportions are associated with increasing methylation, and after controlling for this, methylation decreases with age on average.Figure 4.

Bottom Line: There were no consistent associations of gestational weight gain with offspring DNA methylation.Our data suggest that both maternal obesity and, to a larger degree, underweight affect the neonatal epigenome via an intrauterine mechanism, but weight gain during pregnancy has little effect.We found some evidence that associations of maternal underweight with lower offspring adiposity and maternal obesity with greater offspring adiposity may be mediated via increased DNA methylation.

View Article: PubMed Central - PubMed

Affiliation: MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK, School of Social and Community Medicine, University of Bristol, Bristol, UK and gemma.sharp@bristol.ac.uk.

No MeSH data available.


Related in: MedlinePlus