RT Journal Article
SR Electronic
T1 Multiple sclerosis risk variants regulate gene expression in innate and adaptive immune cells
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000650
DO 10.26508/lsa.202000650
VO 3
IS 7
A1 Gresle, Melissa M
A1 Jordan, Margaret A
A1 Stankovich, Jim
A1 Spelman, Tim
A1 Johnson, Laura J
A1 Laverick, Louise
A1 Hamlett, Alison
A1 Smith, Letitia D
A1 Jokubaitis, Vilija G
A1 Baker, Josephine
A1 Haartsen, Jodi
A1 Taylor, Bruce
A1 Charlesworth, Jac
A1 Bahlo, Melanie
A1 Speed, Terence P
A1 Brown, Matthew A
A1 Field, Judith
A1 Baxter, Alan G
A1 Butzkueven, Helmut
YR 2020
UL http://www.life-science-alliance.org/content/3/7/e202000650.abstract
AB 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.