ArticleNeurology(R) neuroimmunology & neuroinflammation2025
Genetic Risk Variants for Multiple Sclerosis and Other Loci Linked to Intrathecal Immunoglobulin G Synthesis.
Article in Neurology(R) neuroimmunology & neuroinflammation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- EpiATLAS - a reference for human epigenomic research.bioRxiv : the preprint server for biology · 2026Article
- Genetic Prognostic Factors in Multiple Sclerosis: Key Discoveries and Unmet Needs.International journal of molecular sciences · 2026Review
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Authors and funding
37 authors.
Funding
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Abstract
BACKGROUND AND
objectivesIntrathecal synthesis of immunoglobulin G (IgG) is a key feature of multiple sclerosis (MS) and a prognostic marker for the disease course. Although previous studies identified 2 genetic regions-the major histocompatibility complex (MHC) region on chromosome 6 and the immunoglobulin heavy chain constant (IGHC) locus on chromosome 14-associated with intrathecal IgG synthesis in MS, the genetic underpinnings remain insufficiently understood.
methodsWe conducted a genome-wide association study on intrathecal IgG synthesis using the IgG index to identify individuals with (≥0.7) or without (<0.7) quantitative intrathecal synthesis. We used logistic regression models adjusting for sex, age, and population structure. We performed secondary analyses to examine associations between identified loci and the extent of intrathecal IgG synthesis and the presence and extent of intrathecal immunoglobulin A and M synthesis. We further conducted association analyses for imputed human leukocyte antigen alleles and analyzed whether a higher genetic burden for MS risk-quantified through polygenic risk scores-is associated with intrathecal IgG synthesis.
resultsIn the discovery cohort (n = 3,934), we identified a novel genome-wide significant association of the intronic variant rs844586 ( DISCUSSION: Our study revealed a previously unknown association between an intronic variant in
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