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Age-dependent changes in mean and variance of gene expression across tissues in a twin cohort

Research output: Contribution to journalArticle

Ana Viñuela, Andrew A. Brown, Alfonso Buil, Pei-Chien Tsai, Matthew N Davies, Jordana Tzenova Bell, Emmanouil T Dermitzakis, Timothy D Spector, Kerrin S. Small

Original languageEnglish
Pages (from-to)732–741
JournalHuman Molecular Genetics
Volume27
Issue number4
Early online date8 Dec 2017
DOIs
Publication statusPublished - 15 Feb 2018

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Abstract

Changes in mean and variance of gene expression with age have consequences for healthy aging and disease development. Age-dependent changes in phenotypic variance have been associated to a decline in regulatory functions leading to increase in disease risk. Here we investigate age-related mean and variance changes in gene expression measured by RNA-seq of fat, skin, whole blood and derived lymphoblastoid cell lines (LCLs) expression from 855 adult female twins. We see evidence of up to 60% of age effects on transcription levels shared across tissues, and 47% of those on splicing. Using gene expression variance and discordance between genetically identical MZ twin pairs, we identify 137 genes with age-related changes in variance and 42 genes with age-related discordance between co-twins; implying the latter are driven by environmental effects. We identify four eQTLs whose effect on expression is age-dependent (FDR 5%). Combined, these results show a complicated mix of environmental and genetically driven changes in expression with age. Using the twin structure in our data, we show that additive genetic effects explain considerably more of the variance in gene expression than aging, but less that other environmental factors, potentially explaining why reliable expression-derived biomarkers for healthy-aging have proved elusive compared to those derived from methylation.

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