Potential causal and temporal relationship between plasma triglyceride levels and circulating leukocyte

Area of Science:

• Cardiovascular Science
• Immunology
• Genetics

Background:

• Circulating triglyceride (TG) levels and leukocyte counts are key vascular components.
• Their interrelationship and contribution to atherosclerosis are not fully understood.
• The causal link between plasma TG and leukocyte counts requires clarification.

Purpose of the Study:

• To investigate the potential causal relationship between plasma triglyceride levels and leukocyte counts, including subtypes.
• To examine the temporal dynamics between TG levels and leukocyte counts using longitudinal data.

Main Methods:

• Bidirectional Mendelian randomization (MR) analysis was employed.
• A cross-lagged panel model (CLPM) was fitted using data from 13,389 adults over 4 years.
• Genetic variants associated with TG levels and leukocyte counts were utilized.

Main Results:

• Genetically predicted TG levels associated positively with total leukocyte counts (TLC), lymphocyte counts (LC), and neutrophil counts (NC).
• Genetically predicted TLC, LC, and NC associated positively with plasma TG levels.
• After mutual adjustment in MR, only LC showed a significant association with TG levels.
• CLPM indicated a stronger temporal effect of leukocytes on TG levels than vice versa.
• No association was found between TG levels and monocyte, basophil, or eosinophil counts.

Conclusions:

• Plasma TG levels have a causal association with TLC, LC, and NC.
• Lymphocyte counts exhibit a significant positive association with plasma TG levels.
• Elevated circulating lymphocyte counts may precede increases in plasma TG levels, suggesting a potential early marker.