RT Journal Article
SR Electronic
T1 Tissue-specific impacts of aging and genetics on gene expression patterns in humans
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.11.16.468753
DO 10.1101/2021.11.16.468753
A1 Ryo Yamamoto
A1 Ryan Chung
A1 Juan Manuel Vazquez
A1 Huanjie Sheng
A1 Philippa Steinberg
A1 Nilah M Ioannidis
A1 Peter H Sudmant
YR 2021
UL http://biorxiv.org/content/early/2021/11/19/2021.11.16.468753.abstract
AB Age is the primary risk factor for many common human diseases including heart disease, Alzheimer’s dementias, cancers, and diabetes. Determining how and why tissues age differently is key to understanding the onset and progression of such pathologies. Here, we set out to quantify the relative contributions of genetics and aging to gene expression patterns from data collected across 27 tissues from 948 humans. We show that gene expression patterns become more erratic with age in several different tissues reducing the predictive power of expression quantitative trait loci. Jointly modelling the contributions of age and genetics to transcript level variation we find that the heritability (h2) of gene expression is largely consistent among tissues. In contrast, the average contribution of aging to gene expression variance varied by more than 20-fold among tissues with in 5 tissues. We find that the coordinated decline of mitochondrial and translation factors is a widespread signature of aging across tissues. Finally, we show that while in general the force of purifying selection is stronger on genes expressed early in life compared to late in life as predicted by Medawar’s hypothesis, a handful of highly proliferative tissues exhibit the opposite pattern. In contrast, gene expression variation that is under genetic control is strongly enriched for genes under relaxed constraint. Together we present a novel framework for predicting gene expression phenotypes from genetics and age and provide insights into the tissue-specific relative contributions of genes and the environment to phenotypes of aging.Competing Interest StatementThe authors have declared no competing interest.