Glucose-Related Genetic Risk Score and Its Association With Cerebrovascular Abnormality, White-Matter Hyperintensity...

Area of Science:

• Neuroimaging
• Genetics
• Public Health

Background:

• Cerebral white-matter hyperintensities (WMH) are key indicators of stroke, cardiovascular disease, and mortality.
• Previous genetic studies on WMH have not specifically targeted the Han Chinese population or explored links to glucose regulation.
• Understanding genetic influences on WMH is crucial for identifying at-risk individuals and developing targeted interventions.

Purpose of the Study:

• To investigate the association between a genetic risk score (GRS) derived from glucose-related genetic loci and cerebrovascular abnormalities, WMH volume, and brain microstructure.
• To specifically examine these associations within the Han Chinese population.

Main Methods:

• A community-based family study involving 345 participants aged 65 years and older.
• Brain magnetic resonance imaging (MRI) was used to measure WMH volume and brain microstructure (fractional anisotropy and mean diffusivity).
• Genome-wide association study (GWAS) data was utilized to calculate GRSs based on 194 glucose-associated single-nucleotide polymorphisms (SNPs).
• Generalized linear models with generalized estimating equations were employed for statistical analysis.

Main Results:

• Both unweighted and weighted GRSs showed significant associations with cerebrovascular abnormality, WMH volume, and brain microstructure (FA and MD) in the corticospinal tracts and cingulate gyri.
• The association between GRS and mean diffusivity in the left cingulate gyrus was not significant after multivariable adjustment.
• These findings were observed across four specific brain regions, highlighting widespread effects.

Conclusions:

• Genetic loci associated with glucose regulation are significantly linked to MRI-measured brain abnormalities, including WMH and altered brain microstructure.
• This research offers novel insights into the genetic underpinnings of brain injury and its progression, particularly in relation to metabolic factors.
• The findings emphasize the importance of considering glucose metabolism in the context of cerebrovascular health and brain aging.