Genome-wide association analyses highlight the neuronal contribution to multiple sclerosis susceptibility.

Inhibitory neurons are a key target in MS susceptibility, with seven loci, including STAT3, showing altered expression exclusively in these cells.

• Why it matters: Understanding the neuronal contribution to MS is crucial because most genetic studies focus on immune cells, leaving the neuronal role less clear, which could reveal new therapeutic targets.
• What they did: A multi-ancestry genome-wide association study involving over 750,000 individuals identified 236 susceptibility variants, including four novel loci, and integrated single-cell data to pinpoint 76 candidate causal genes.
• The result: Findings suggest MS risk involves reduced CNS resilience, with neuronal pathways, especially involving STAT3, influencing disease susceptibility and potentially affecting cognition and white matter integrity.