The dysregulation of 3 genes may increase the risk of developing multiple sclerosis (MS), according to a new study published in the Annals of Clinical and Translational Neurology.

This finding sheds light on the pathogenesis of MS and identifies potential new targets for future therapeutic research.

To identify new genes that may be involved in MS risk and analyze their expression in the brain, a team of researchers from China led by Chengcheng Zhang from the Mental Health Center and Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University in Chengdu conducted a 2-stage proteome-wide association study (PWAS).

Continue Reading

The team first integrated data from a genome-wide association study (GWAS) including more than 40,000 individuals with MS and controls with 2 different human brain proteomes from the dorsolateral prefrontal cortex.

Then they conducted colocalization analysis for the GWAS and protein quantitative trait loci signals to identify candidate genes. They identified 51 genes, the protein abundance of which was associated with the risk of MS. 

Read more about the pathophysiology of MS

Of these 51 genes, 18 overlapped in the discovery and confirmation PWAS. The colocalization analysis identified 6 causal genes with genetic variants for the risk of MS. Of these 6 genes, 3 (SHMT1, FAM120B, and ICA1L) had dysregulated expression in the brain.

When they further analyzed the expression of these 3 genes, the researchers found that SHMT1 was significantly upregulated in white matter lesions, while FAM120B was upregulated in normal-appearing white matter and white matter lesions. ICA1L was downregulated in normal-appearing gray matter and grey matter lesions.

“Dysregulation of SHMT1, FAM120B, and ICA1L may confer MS risk,” the researchers wrote. “Our results . . . prioritized unique protein biomarkers and potential therapeutic targets that could aid in MS diagnosis and advance the development of new intervention.”


Jia T, Ma Y, Qin F, Han F, Zhang C. Brain proteome-wide association study linking-genes in multiple sclerosis pathogenesis. Ann Clin Transl Neurol. Published online December 7, 2022. doi:10.1002/acn3.51699