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

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.