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

Lookup NU author(s): Dr Ana Viñuela

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© The Author(s) 2017.Changes in the 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 with 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 with those derived from methylation.


Publication metadata

Author(s): Vinuela A, Brown AA, Buil A, Tsai P-C, Davies MN, Bell JT, Dermitzakis ET, Spector TD, Small KS

Publication type: Article

Publication status: Published

Journal: Human Molecular Genetics

Year: 2018

Volume: 27

Issue: 4

Pages: 732-741

Online publication date: 08/12/2017

Acceptance date: 29/11/2017

Date deposited: 19/06/2020

ISSN (print): 0964-6906

ISSN (electronic): 1460-2083

Publisher: Oxford University Press

URL: https://doi.org/10.1093/hmg/ddx424

DOI: 10.1093/hmg/ddx424

PubMed id: 29228364


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