Genetic correlations of brain lesion distribution in multiple sclerosis: an exploratory study

Area of Science:

• Neuroimmunology
• Genetics of Multiple Sclerosis
• Neuroimaging

Background:

• Multiple sclerosis (MS) exhibits significant inter-individual variability in brain lesion volume and spatial distribution.
• The role of genetic predisposition in shaping the spatial patterns of white matter lesions in MS remains incompletely understood.

Purpose of the Study:

• To investigate the association between candidate gene single nucleotide polymorphisms (SNPs) and the spatial distribution of white matter brain lesions in patients with MS.
• To identify specific genetic variants that may influence where lesions develop in the brain.

Main Methods:

• Genotyping of 69 SNPs in 208 MS patients using a DNA chip.
• Manual outlining of T2 brain lesions on MRI scans to create binary lesion masks.
• Voxelwise nonparametric general linear model (GLM) analysis using Randomise software to relate lesion distribution to genotype, followed by clusterwise analysis.

Main Results:

• Eleven SNPs showed significant associations between genotype and spatial clusters of lesion probability in various brain regions, particularly periventricular areas.
• After controlling for total brain lesion volume, only the SNP rs2227139, located in the MHC class II region, remained significantly associated with lesion distribution.
• The heterozygote genotype for rs2227139 was linked to a significant increase in lesion probability within the right frontal periventricular region.

Conclusions:

• Heterozygosity for the rs2227139 SNP in the MHC class II region is associated with an increased probability of periventricular lesions in the right frontal lobe in MS patients.
• The spatial distribution patterns of MS lesions are influenced by genetic factors, with some associations being partly explained by overall lesion burden.