Time-dependent genetic effects on gene expression implicate aging processes.
Time-dependent genetic effects on gene expression implicate aging processes.
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DOI：
10.1101/gr.207688.116
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发表时间：
2017-04
期刊：
影响因子：
7
通讯作者：
Dermitzakis ET
中科院分区：
文献类型：
--
作者：
Bryois J;Buil A;Ferreira PG;Panousis NI;Brown AA;Viñuela A;Planchon A;Bielser D;Small K;Spector T;Dermitzakis ET
基因的表达依赖于遗传和环境因素。在过去的十年里，大量的研究大大提高了我们对基因表达的遗传结构的理解。然而，目前尚不清楚基因表达的遗传效应是否会随着时间的推移保持稳定。在这里，我们使用来自双胞胎队列的纵向全血基因表达数据表明，随着时间的推移，基因子集的遗传结构是不稳定的。此外，我们确定了2213个在研究中和跨研究中与衰老有关的时间点差异表达的基因。有趣的是，我们发现大多数差异表达的基因受到77个假定因果基因的影响。最后，我们观察到假定的因果基因和下调的基因受到时间点之间基因控制丧失的影响。综上所述，我们的数据表明，基因子集的遗传结构不稳定可能会导致对带有衰老特征的转录组的广泛影响。
Gene expression is dependent on genetic and environmental factors. In the last decade, a large body of research has significantly improved our understanding of the genetic architecture of gene expression. However, it remains unclear whether genetic effects on gene expression remain stable over time. Here, we show, using longitudinal whole-blood gene expression data from a twin cohort, that the genetic architecture of a subset of genes is unstable over time. In addition, we identified 2213 genes differentially expressed across time points that we linked with aging within and across studies. Interestingly, we discovered that most differentially expressed genes were affected by a subset of 77 putative causal genes. Finally, we observed that putative causal genes and down-regulated genes were affected by a loss of genetic control between time points. Taken together, our data suggest that instability in the genetic architecture of a subset of genes could lead to widespread effects on the transcriptome with an aging signature.