Multiple Sclerosis risk variants regulate gene expression in innate and adaptive immune cells

Gresle, Melissa M., Jordan, Margaret A., Stankovich, Jim, Spelman, Tim, Johnson, Laura J., Laverick, Louise, Hamlett, Alison, Smith, Letitia D., Jokubaitis, Vilija G., Baker, Josephine, Haartsen, Jodi, Taylor, Bruce, Charlesworth, Jac, Bahlo, Melanie, Speed, Terence P., Brown, Matthew A., Field, Judith, Baxter, Alan G., and Butzkueven, Helmut (2020) Multiple Sclerosis risk variants regulate gene expression in innate and adaptive immune cells. Life Science Alliance, 3 (7). e202000650.

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Abstract

At least 200 single-nucleotide polymorphisms (SNPs) are associated with multiple sclerosis (MS) risk. A key function that could mediate SNP-encoded MS risk is their regulatory effects on gene expression. We performed microarrays using RNA extracted from purified immune cell types from 73 untreated MS cases and 97 healthy controls and then performed Cis expression quantitative trait loci mapping studies using additive linear models. We describe MS risk expression quantitative trait loci associations for 129 distinct genes. By extending these models to include an interaction term between genotype and phenotype, we identify MS risk SNPs with opposing effects on gene expression in cases compared with controls, namely, rs2256814 MYT1 in CD4 cells (q = 0.05) and rs12087340 RF00136 in monocyte cells (q = 0.04). The rs703842 SNP was also associated with a differential effect size on the expression of the METTL21B gene in CD8 cells of MS cases relative to controls (q = 0.03). Our study provides a detailed map of MS risk loci that function by regulating gene expression in cell types relevant to MS.

Item ID: 63614
Item Type: Article (Research - C1)
ISSN: 2575-1077
Keywords: Multiple sclerosis, risk variants, gene expression regulation, immune cells
Copyright Information: © 2020 Gresle et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
Funders: Rebecca L Cooper Medical Research Foundation, Lion's Club of Australia, NHMRC
Projects and Grants: MSRA 15-025
Research Data: https://www.ebi.ac.uk/ega/about/access/EGAS00001004087
Date Deposited: 09 Jul 2020 05:06
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110706 Immunogenetics (incl Genetic Immunology) @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 25%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920111 Nervous System and Disorders @ 25%
97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 50%
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