Evidence for genetic correlation between human cerebral white matter microstructure and inflammation

Area of Science:

• Neuroscience
• Immunology
• Genetics

Background:

• Immune system activity, specifically pro-inflammatory cytokines, affects white matter microstructure.
• Both white matter microstructure and inflammatory markers exhibit significant heritability.
• The overlap in genetic factors influencing these traits in humans remains largely unexplored.

Purpose of the Study:

• To investigate the genetic correlations between white matter microstructure and circulating pro-inflammatory cytokines (IL-6, IL-8, TNFα).
• To determine if shared genetic factors underlie the observed phenotypic associations between brain structure and inflammation.

Main Methods:

• Utilized genetic correlation analyses on extended pedigrees from the Genetics of Brain Structure and Function Study (N=1862).
• Assessed white matter microstructure using fractional anisotropy (FA) from diffusion tensor imaging (DTI).
• Quantified serum levels of IL-6, IL-8, and TNFα.

Main Results:

• Phenotypically, higher inflammatory marker levels correlated with lower FA values across the brain.
• Significant negative genetic correlations were found between most DTI measures and IL-8 and TNFα.
• Genetic correlations between DTI measures and IL-6 were not significant; TNFα effects diminished when controlling for BMI.

Conclusions:

• Shared genetic factors may link certain inflammatory markers, like IL-8 and TNFα, with white matter microstructure.
• Findings suggest a genetic basis for the interplay between inflammation and brain structure.
• Further research into these genetic correlations can refine understanding of inflammatory processes in brain structure.