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Genome Res. 2017 Apr;27(4):545-552. doi: 10.1101/gr.207688.116. Epub 2017 Mar 16.

Time-dependent genetic effects on gene expression implicate aging processes.

Bryois J1,2,3, Buil A1,2,3, Ferreira PG1,2,3, Panousis NI1,2,3, Brown AA1,2,3, Viñuela A1,2,3,4, Planchon A1,2,3, Bielser D1,2,3, Small K4, Spector T4, Dermitzakis ET1,2,3.

Author information

Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva 4, Switzerland.
Institute of Genetics and Genomics in Geneva (iGE3), 1211 Geneva 4, Switzerland.
Swiss Institute of Bioinformatics (SIB), 1211 Geneva 4, Switzerland.
Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, United Kingdom.


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.

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