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

Ryo Yamamoto, Ryan Chung, Juan Manuel Vazquez, Huanjie Sheng, Philippa L. Steinberg, Nilah M. Ioannidis () and Peter H. Sudmant ()
Additional contact information
Ryo Yamamoto: University of California Berkeley
Ryan Chung: University of California Berkeley
Juan Manuel Vazquez: University of California Berkeley
Huanjie Sheng: University of California Berkeley
Philippa L. Steinberg: University of California Berkeley
Nilah M. Ioannidis: University of California Berkeley
Peter H. Sudmant: University of California Berkeley

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract 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 (h2) is consistent among tissues while the contribution of aging varies by >20-fold with $${R}_{{{{{{{{\rm{age}}}}}}}}}^{2} \; > \;{h}^{2}$$ 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.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-33509-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33509-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-33509-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().