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Longitudinal study of gene expression in a Swedish population sample

Banff International Research Station for Mathematical Innovation and Discovery

Background: While DNA sequence is more or less stable throughout life, gene regulation and expression is dynamic, fluctuating in response to different exposures. Increased knowledge about how genes are regulated and expressed, and how this changes over time can give important insights to fundamental questions about gene function. Methods: We sequenced the blood transcriptomes of 65 individuals at both age 70 and 80 (130 samples) for which genotype information was available. We investigated genome-wide changes in gene expression and regulation with age. Results: We identified 4,414 genes showing differential expression with age (2,388 up- and 2,026 down-regulated with age), and strong enrichment for age related GO terms (immune and stress response) and KEGG pathways (longevity and metabolic pathways). Moreover, we found 1,562 and 1,489 eGenes (genes with an eQTL), at age 70 and 80. The difference in the proportion of eGenes between 70 and 80 year old samples was significant (p-value=8.8e-03) Together, these results indicate that, (1) gene expression increases with age and (2) while genetic regulation of gene expression is stable over time for most genes, it is reduced for other genes at a later age. Significance: In summary, we have performed one of the first long-term longitudinal studies of genetics of gene expression that highlights transcriptome dynamics late in life.

Mathematics; Statistics; Biology and other natural sciences

video/mp4

Author affiliation: Stanford University

2017-09-24

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/63100

Unreviewed

http://creativecommons.org/licenses/by-nc-nd/4.0/