A Genetic Risk Variant for Multiple Sclerosis Severity is Associated with Brain Atrophy

Area of Science:

• Neuroimmunology
• Genetics
• Neuroimaging

Background:

• The DYSF-ZNF638 locus harbors a genetic variant, rs10191329, previously associated with poor long-term clinical outcomes in multiple sclerosis (MS).
• Understanding the impact of genetic factors on disease progression in MS is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the association between the rs10191329 genetic variant and brain atrophy in individuals with relapsing MS.
• To determine if rs10191329 can serve as a biomarker for disease progression in MS.

Main Methods:

• Magnetic resonance imaging (MRI) was used to measure brain atrophy.
• A discovery cohort of 748 MS patients and a replication cohort of 360 MS patients were analyzed.
• Statistical analyses were performed to assess the association between the rs10191329 minor allele (A) and brain atrophy rates.

Main Results:

• A significant association was observed between the rs10191329*A allele and increased brain atrophy.
• Patients carrying the rs10191329*A allele exhibited approximately 28% more brain atrophy.
• These findings were consistent across both the discovery and replication cohorts.

Conclusions:

• The rs10191329 genetic variant is associated with accelerated brain atrophy in relapsing multiple sclerosis.
• Stratification of patients based on rs10191329 status may be beneficial for clinical trials in MS.
• Further research into the mechanisms underlying this association could reveal novel therapeutic targets for MS.