Differential white blood cell count and epigenetic clocks: a bidirectional Mendelian randomization study

Area of Science:

• Genetics
• Immunology
• Aging Research

Background:

• Human aging and white blood cell (WBC) counts are complex traits influenced by genetics.
• Epigenetic clocks predict chronological age, but their bidirectional relationship with WBC counts is underexplored.

Purpose of the Study:

• To investigate the bidirectional causal effects between epigenetic clocks and WBC counts.
• To determine if specific WBC types influence epigenetic age acceleration.

Main Methods:

• Mendelian randomization (MR) analysis using summary statistics from four epigenetic clocks and the Blood Cell Consortium.
• Employed random-effects inverse-variance weighted method and multivariate MR.

Main Results:

• Decreased lymphocyte count accelerated PhenoAge, GrimAge, and HannumAge.
• Increased neutrophil count elevated PhenoAge, GrimAge, and HannumAge.
• No significant causal impact of epigenetic clocks on overall WBC counts was found.

Conclusions:

• Lymphocyte and neutrophil counts have independent causal effects on accelerating epigenetic aging (PhenoAge, GrimAge, HannumAge).
• WBCs play a critical role in influencing epigenetic clocks.
• Immune parameters are important for interpreting epigenetic age.