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.
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.
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孕产妇怀孕前BMI和妊娠体重增加，后代DNA甲基化和后代肥胖：来自父母和孩子的雅芳纵向研究的结果。
DOI：
10.1093/ije/dyv042
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发表时间：
2015-08
影响因子：
7.7
通讯作者：
Relton CL
中科院分区：
文献类型：
--
作者：
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
背景：有证据表明，子宫内营养不良和营养过剩可能会影响以后的肥胖。表观遗传修饰被认为是一种合理的调节机制。方法：我们使用多变量线性回归和阴性对照设计来检查 1018 名参与者的后代表观基因组 DNA 甲基化与母体和后代肥胖的关系。结果：与正常体重母亲的新生儿相比，肥胖和体重不足母亲的后代分别有 28 个和 1621 个 CpG 位点差异甲基化[错误发现率（FDR）校正 P 值 < 0.05），与母亲肥胖和体重不足相关的位点没有重叠。在 78.6% 的与肥胖相关的位点和 87.9% 的与体重不足相关的位点中发现了正相关，即较高的甲基化与超出正常范围的体重指数 (BMI) 相关。母亲肥胖与后代甲基化的关联强于父亲肥胖的关联，支持宫内机制。妊娠期体重增加与后代 DNA 甲基化没有一致的关联。一般来说，与母亲肥胖相关的高甲基化位点或与母亲体重不足相关的低甲基化位点往往与后代肥胖呈正相关，而与母亲肥胖相关的低甲基化或与母亲体重不足相关的高甲基化位点往往与后代肥胖呈负相关。结论：我们的数据表明，母亲肥胖以及在更大程度上体重不足都通过宫内机制影响新生儿表观基因组，但妊娠期间体重增加影响不大。我们发现一些证据表明，母亲体重过轻与后代肥胖程度较低以及母亲肥胖与后代肥胖程度较高之间的关联可能是通过 DNA 甲基化增加来介导的。
Background: Evidence suggests that in utero exposure to undernutrition and overnutrition might affect adiposity in later life. Epigenetic modification is suggested as a plausible mediating mechanism. Methods: We used multivariable linear regression and a negative control design to examine offspring epigenome-wide DNA methylation in relation to maternal and offspring adiposity in 1018 participants. Results: Compared with neonatal offspring of normal weight mothers, 28 and 1621 CpG sites were differentially methylated in offspring of obese and underweight mothers, respectively [false discovert rate (FDR)-corrected P-value < 0.05), with no overlap in the sites that maternal obesity and underweight relate to. A positive association, where higher methylation is associated with a body mass index (BMI) outside the normal range, was seen at 78.6% of the sites associated with obesity and 87.9% of the sites associated with underweight. Associations of maternal obesity with offspring methylation were stronger than associations of paternal obesity, supporting an intrauterine mechanism. There were no consistent associations of gestational weight gain with offspring DNA methylation. In general, sites that were hypermethylated in association with maternal obesity or hypomethylated in association with maternal underweight tended to be positively associated with offspring adiposity, and sites hypomethylated in association with maternal obesity or hypermethylated in association with maternal underweight tended to be inversely associated with offspring adiposity. Conclusions: 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.