Time-dependent genetic effects on gene expression implicate aging processes
- Julien Bryois1,2,3,
- Alfonso Buil1,2,3,
- Pedro G. Ferreira1,2,3,
- Nikolaos I. Panousis1,2,3,
- Andrew A. Brown1,2,3,
- Ana Viñuela1,2,3,4,
- Alexandra Planchon1,2,3,
- Deborah Bielser1,2,3,
- Kerrin Small4,
- Tim Spector4 and
- Emmanouil T. Dermitzakis1,2,3
- 1Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva 4, Switzerland;
- 2Institute of Genetics and Genomics in Geneva (iGE3), 1211 Geneva 4, Switzerland;
- 3Swiss Institute of Bioinformatics (SIB), 1211 Geneva 4, Switzerland;
- 4Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, United Kingdom
- Corresponding author: emmanouil.dermitzakis{at}unige.ch
Abstract
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.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.207688.116.
- Received March 30, 2016.
- Accepted January 23, 2017.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
