Multi-ancestry study links 236 MS risk variants to inhibitory neurons
Researchers analyzing 20,831 multiple sclerosis cases and 729,220 controls have identified 236 susceptibility variants outside the major histocompatibility complex. The multi-ancestry genome-wide study, published in Nature Genetics, found four novel genomic loci. By integrating single-cell data from blood and brain tissue, the team pinpointed 76 candidate causal genes. Inhibitory neurons emerged as a key target cell type. Seven loci, including STAT3, showed altered expression only in these cells. The STAT3 variant also correlated with cognition and white matter integrity in people without MS.
The findings suggest multiple sclerosis susceptibility may reflect reduced resilience of the central nervous system to inflammatory challenges.
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