Genetic and environmental influences interact with age and sex in shaping the human methylome.
Genetic and environmental influences interact with age and sex in shaping the human methylome.
复制标题
DOI：
10.1038/ncomms11115
复制
发表时间：
2016-04-07
影响因子：
16.6
通讯作者：
Boomsma DI
中科院分区：
文献类型：
--
作者：
van Dongen J;Nivard MG;Willemsen G;Hottenga JJ;Helmer Q;Dolan CV;Ehli EA;Davies GE;van Iterson M;Breeze CE;Beck S;BIOS Consortium;Suchiman HE;Jansen R;van Meurs JB;Heijmans BT;Slagboom PE;Boomsma DI
甲基化组受到遗传和环境的影响。它们的影响可能取决于性别和年龄，导致与性别和年龄有关的生理变化和疾病易感性。在这里，我们估计了全血中DNA甲基化水平的总遗传力，并估计了来自双胞胎家庭的2，603个个体中411，169个位点的常见单核苷酸多态性所解释的方差，以建立DNA甲基化个体间变异的目录。遗传力估计值在整个基因组中各不相同（平均值=19%），交互作用分析揭示了数千个具有性别特异性遗传力的位点以及环境方差随年龄增加的位点。与先前发表的数据相结合，说明了基因组和环境在与代谢性状、吸烟和衰老相关的甲基化位点上对整个生命周期的影响。这些发现表明，我们的目录中包含了关于基因组位置的有价值的信息，在这些位置上，人与人之间的甲基化变异可能反映了与疾病相关的环境暴露或遗传变异。 遗传和环境对DNA甲基化的不同影响可能导致与性别和年龄相关的生理变化和疾病易感性。通过分析来自双胞胎家庭的2，603个个体的DNA甲基化组，作者建立了DNA甲基化个体间变异的目录。
The methylome is subject to genetic and environmental effects. Their impact may depend on sex and age, resulting in sex- and age-related physiological variation and disease susceptibility. Here we estimate the total heritability of DNA methylation levels in whole blood and estimate the variance explained by common single nucleotide polymorphisms at 411,169 sites in 2,603 individuals from twin families, to establish a catalogue of between-individual variation in DNA methylation. Heritability estimates vary across the genome (mean=19%) and interaction analyses reveal thousands of sites with sex-specific heritability as well as sites where the environmental variance increases with age. Integration with previously published data illustrates the impact of genome and environment across the lifespan at methylation sites associated with metabolic traits, smoking and ageing. These findings demonstrate that our catalogue holds valuable information on locations in the genome where methylation variation between people may reflect disease-relevant environmental exposures or genetic variation. Differential impact of genetic and environmental influences on DNA methylation may result in sex- and age-related physiological variation and disease susceptibility. By analysing DNA methylome of 2,603 individuals from twin families, here, the authors establish a catalogue of between-individual variation in DNA methylation.