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Causal relationships between Epstein-Barr virus infection and sarcopenia: A bidirectional Mendelian randomization

Meiqi Yin1, Jin Ma2, Rongchun Li3

  • 1Department of Endocrinology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, China; Department of Endocrinology, Suqian TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suqian, Jiangsu, China.

Archives of Gerontology and Geriatrics
|July 30, 2025
PubMed
Abstract

Insights

Epstein-Barr virus (EBV) EBNA-1 and ZEBRA antibodies are causally linked to sarcopenia development, impacting muscle mass and walking speed. This suggests EBV serology can help identify individuals at risk for sarcopenia.

Area of Science:

  • Genetics
  • Immunology
  • Gerontology

Background:

  • Sarcopenia, characterized by age-related loss of muscle mass, strength, and function, has unclear links with Epstein-Barr virus (EBV) infections.
  • Understanding potential etiological factors for sarcopenia is crucial for developing effective interventions.

Purpose of the Study:

  • To investigate the potential causal relationship between EBV-specific antibody traits and sarcopenia using a bidirectional Mendelian randomization (MR) approach.
  • To explore whether sarcopenia traits influence EBV serology.

Main Methods:

  • A bidirectional MR study utilized generalized summary-based MR (GSMR) and inverse-variance weighted (IVW) analyses.
  • Instrumental variables for EBV antibodies (EA-D, EBNA-1, VCA p18, ZEBRA) and sarcopenia traits were rigorously selected to minimize pleiotropy.
  • Sensitivity analyses and mediation analysis were performed to validate findings and explore potential immune cell involvement.

Main Results:

  • Elevated EBV EBNA-1 antibody levels causally associated with reduced walking speed.
  • Increased EBV ZEBRA antibody levels causally associated with decreased appendicular lean mass.
  • Reverse MR indicated whole body fat-free mass may increase EBV VCA p18 antibodies, with potential mediation by certain immunophenotypes.

Conclusions:

  • EBV EBNA-1 and ZEBRA antibodies are identified as causal risk factors for sarcopenia.
  • EBV serology shows promise as a biomarker for sarcopenia risk stratification and potential therapeutic targeting.
Keywords:
CausalityEpstein–Barr virusGWASMendelian randomizationSarcopenia

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