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The genetic control of gene expression changes over time, particularly with aging. This instability affects many genes and may be driven by a small set of causal genes.

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Area of Science:

  • Genetics
  • Molecular Biology
  • Aging Research

Background:

  • Gene expression is influenced by genetic and environmental factors.
  • Understanding the genetic architecture of gene expression has advanced, but its stability over time is not well understood.

Purpose of the Study:

  • To investigate the temporal stability of the genetic architecture of gene expression.
  • To identify genes and genetic factors associated with age-related changes in gene expression.

Main Methods:

  • Analysis of longitudinal whole-blood gene expression data from a twin cohort.
  • Identification of differentially expressed genes and putative causal genes across time points.
  • Investigation of changes in genetic control over time.

Main Results:

  • The genetic architecture of a subset of genes is unstable over time.
  • 2213 genes were differentially expressed across time points and linked to aging.
  • A subset of 77 putative causal genes influenced most differentially expressed genes.
  • Putative causal and down-regulated genes showed a loss of genetic control over time.

Conclusions:

  • Temporal instability in gene expression's genetic architecture affects a subset of genes.
  • These changes are linked to aging and may be driven by specific causal genes.
  • Loss of genetic control over time contributes to widespread transcriptome alterations with an aging signature.