Prenatal and early life influences on epigenetic age in children: a study of mother-offspring pairs from two cohort studies.
Prenatal and early life influences on epigenetic age in children: a study of mother-offspring pairs from two cohort studies.
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DOI：
10.1093/hmg/ddv456
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发表时间：
2016-01-01
影响因子：
3.5
通讯作者：
Smith GD
中科院分区：
文献类型：
--
作者：
Simpkin AJ;Hemani G;Suderman M;Gaunt TR;Lyttleton O;Mcardle WL;Ring SM;Sharp GC;Tilling K;Horvath S;Kunze S;Peters A;Waldenberger M;Ward-Caviness C;Nohr EA;Sørensen TI;Relton CL;Smith GD
基于 DNA 甲基化的衰老生物标志物与实际年龄高度相关。甲基化估计年龄与实际年龄的偏差可用于定义儿童发育或成人年龄加速（AA）的表观遗传测量。人们对这些衰老的表观遗传指标的遗传或环境决定因素知之甚少。我们使用 Infinium HumanMmethylation450 BeadChip 获得了雅芳父母和儿童纵向研究中 1018 对母子的五个时间点的 DNA 甲基化谱。使用 Horvath 年龄估计方法，我们计算了这些样本的表观遗传年龄。 AA 被定义为表观遗传年龄回归实际年龄的残差。测试了 AA 与儿童横断面临床变量的关联。我们确定了 AA 与性别、出生体重、剖腹产分娩以及怀孕期间的一些母亲特征（即吸烟、体重、BMI、硒和胆固醇水平）之间的关联。不饮酒者的后代平均有较高的 AA，但这种差异似乎在童年时期就消失了。在 ARIES 中发现的性别、出生体重和 AA 之间的关联在一个独立队列 (GOYA) 中得到了重复。在儿童中，表观遗传 AA 测量值与多个临床相关变量相关，早期生命暴露似乎与青春期 AA 的变化相关。需要对表观遗传衰老进行进一步研究，包括使用因果推理方法，以更好地理解衰老。
DNA methylation-based biomarkers of aging are highly correlated with actual age. Departures of methylation-estimated age from actual age can be used to define epigenetic measures of child development or age acceleration (AA) in adults. Very little is known about genetic or environmental determinants of these epigenetic measures of aging. We obtained DNA methylation profiles using Infinium HumanMethylation450 BeadChips across five time-points in 1018 mother–child pairs from the Avon Longitudinal Study of Parents and Children. Using the Horvath age estimation method, we calculated epigenetic age for these samples. AA was defined as the residuals from regressing epigenetic age on actual age. AA was tested for associations with cross-sectional clinical variables in children. We identified associations between AA and sex, birth weight, birth by caesarean section and several maternal characteristics in pregnancy, namely smoking, weight, BMI, selenium and cholesterol level. Offspring of non-drinkers had higher AA on average but this difference appeared to resolve during childhood. The associations between sex, birth weight and AA found in ARIES were replicated in an independent cohort (GOYA). In children, epigenetic AA measures are associated with several clinically relevant variables, and early life exposures appear to be associated with changes in AA during adolescence. Further research into epigenetic aging, including the use of causal inference methods, is required to better our understanding of aging.