RT Journal
A1 Bryois, Julien
A1 Buil, Alfonso
A1 Ferreira, Pedro G.
A1 Panousis, Nikolaos I.
A1 Brown, Andrew A.
A1 Viñuela, Ana
A1 Planchon, Alexandra
A1 Bielser, Deborah
A1 Small, Kerrin
A1 Spector, Tim
A1 Dermitzakis, Emmanouil T.
T1 Time-dependent genetic effects on gene expression implicate aging processes
JF Genome Research 
JO Genome Research 
YR 2017 
FD April 01 
VO 27 
IS 4 
SP 545 
OP 552 
DO 10.1101/gr.207688.116 
UL http://genome.cshlp.org/content/27/4/545.abstract 
AB 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.