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

Author

Listed:
  • Ryo Yamamoto

    (University of California Berkeley
    University of California Los Angeles)

  • 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
    University of California Berkeley)

  • Peter H. Sudmant

    (University of California Berkeley
    University of California Berkeley)

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.

Suggested Citation

  • Ryo Yamamoto & Ryan Chung & Juan Manuel Vazquez & Huanjie Sheng & Philippa L. Steinberg & Nilah M. Ioannidis & Peter H. Sudmant, 2022. "Tissue-specific impacts of aging and genetics on gene expression patterns in humans," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33509-0
    DOI: 10.1038/s41467-022-33509-0
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