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Identifying Susceptibility Genes and Shared Genetic Architecture for Longevity and Muscle Weakness.

Yilong Lin1,2, Yun Zhang1,3, Shengjie Lin2

  • 1Depeartment of Breast Surgery, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.

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|January 27, 2026
PubMed
Summary

This study identified genes linked to longevity and muscle weakness, revealing shared genetic factors that influence both aging and muscle decline. These findings offer potential targets for promoting healthy aging and reducing disability.

Keywords:
genome‐wide cross‐trait analysislongevitymuscle weaknesssarcopeniashared genetic architecturetranscriptome‐wide association studies

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Area of Science:

  • Genetics
  • Aging Research
  • Molecular Biology

Background:

  • Longevity and muscle strength are heritable traits.
  • Age-related muscle weakness contributes significantly to disability in older adults.
  • Genetic underpinnings of lifespan and sarcopenia are not fully understood.

Purpose of the Study:

  • Identify genes associated with longevity and muscle weakness.
  • Characterize the shared genetic architecture between these traits.
  • Investigate potential molecular targets for healthy aging.

Main Methods:

  • Integrated large-scale genome-wide association studies (GWAS) for longevity and muscle weakness.
  • Utilized Genotype-Tissue Expression (GTEx) v8 eQTL data.
  • Applied transcriptome-wide association studies (TWAS), Mendelian randomization (MR), and colocalization analyses.

Main Results:

  • APOC1 and TOMM40 were associated with longevity; DYM and TGFA with muscle weakness.
  • Higher expression of APOC1/TOMM40 correlated with increased longevity odds.
  • Higher expression of DYM/TGFA correlated with reduced muscle weakness risk.
  • Identified shared causal variants and a negative genetic correlation between longevity and muscle weakness.
  • Discovered pleiotropic genes influencing both longevity and muscle weakness, including the TOMM40/APOE/APOC1 cluster.

Conclusions:

  • Identified key susceptibility genes for longevity and muscle weakness.
  • Uncovered shared genetic loci connecting aging and muscle decline.
  • Provided insights into the genetic architecture of aging phenotypes.
  • Highlighted potential molecular targets for interventions promoting healthy aging and reducing disability.