Tissue-specific impacts of aging and genetics on gene expression patterns in humans

Age is the primary risk factor for many common human diseases. Here, we quantify the relative contributions of genetics and aging to gene expression patterns across 27 tissues from 948 humans. We show that the predictive power of expression quantitative trait loci is impacted by age in many tissues....

Full description

Saved in:
Bibliographic Details
Published in:Nature communications 2022-10, Vol.13 (1), p.5803-12, Article 5803
Main Authors: Yamamoto, Ryo, Chung, Ryan, Vazquez, Juan Manuel, Sheng, Huanjie, Steinberg, Philippa L., Ioannidis, Nilah M., Sudmant, Peter H.
Format: Article
Language:English
Subjects:
631/181/2474
631/208/199
631/208/212/2019
Age
Aging
Aging - genetics
Gene Expression
Gene Expression Regulation
Gene mapping
Genes
Genetic control
Genetic diversity
Genetics
Health risks
Heritability
Humanities and Social Sciences
Humans
multidisciplinary
Mutation
Phenotype
Phenotypes
Quantitative trait loci
Quantitative Trait Loci - genetics
Risk analysis
Risk factors
Science
Science (multidisciplinary)
Tissues
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Age is the primary risk factor for many common human diseases. Here, we quantify the relative contributions of genetics and aging to gene expression patterns across 27 tissues from 948 humans. We show that the predictive power of expression quantitative trait loci is impacted by age in many tissues. Jointly modelling the contributions of age and genetics to transcript level variation we find expression heritability ( h 2 ) is consistent among tissues while the contribution of aging varies by >20-fold with R age 2 > h 2 in 5 tissues. We find that while the force of purifying selection is stronger on genes expressed early versus late in life (Medawar’s hypothesis), several highly proliferative tissues exhibit the opposite pattern. These non-Medawarian tissues exhibit high rates of cancer and age-of-expression-associated somatic mutations. In contrast, genes under genetic control are under relaxed constraint. Together, we demonstrate the distinct roles of aging and genetics on expression phenotypes. Age is a risk factor for many diseases, but the impact of aging on molecular phenotypes is not fully understood. Here, the authors quantify the relative contributions of genetics and aging to gene expression patterns across 27 tissues in humans, showing that age and genetics each play distinct roles in shaping expression phenotypes.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-33509-0