Multiple sclerosis risk variants regulate gene expression in innate and adaptive immune cells
Melissa M Gresle1,2,3, Margaret A Jordan4, Jim Stankovich3
1Department of Medicine, University of Melbourne, Parkville, Australia.
Life Science Alliance
|June 11, 2020
Summary
Multiple sclerosis (MS) risk SNPs can regulate gene expression. This study identified 129 genes associated with MS risk loci and found specific SNPs affecting gene expression in immune cells of MS patients.
Area of Science:
- Genetics
- Immunology
- Neuroscience
Background:
- Over 200 single-nucleotide polymorphisms (SNPs) are linked to multiple sclerosis (MS) risk.
- Gene expression regulation by SNPs is a potential mechanism mediating MS risk.
Purpose of the Study:
- To map MS risk loci by analyzing gene expression.
- To identify specific SNPs that regulate gene expression in immune cells relevant to MS.
Main Methods:
- Microarray analysis of RNA from immune cells of MS cases and healthy controls.
- Cis expression quantitative trait loci (eQTL) mapping using additive linear models.
- Analysis of genotype-phenotype interactions to detect opposing gene expression effects.
Main Results:
- Identified 129 distinct genes with MS risk eQTL associations.
- Discovered SNPs (rs2256814 in MYT1, rs12087340 in RF00136) with opposing effects on gene expression in MS cases vs. controls.
- Found SNP rs703842 with a differential effect on METTL21B gene expression in CD8 cells of MS cases.
Conclusions:
- Provides a comprehensive map of MS risk loci impacting gene expression in relevant cell types.
- Highlights specific SNPs and genes involved in MS pathogenesis through gene regulation.
- Suggests a role for cell-specific gene expression changes in MS.
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