Journal article

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

Melissa M Gresle, Margaret A Jordan, Jim Stankovich, Tim Spelman, Laura J Johnson, Louise Laverick, Alison Hamlett, Letitia D Smith, Vilija G Jokubaitis, Josephine Baker, Jodi Haartsen, Bruce Taylor, Jac Charlesworth, Melanie Bahlo, Terence P Speed, Matthew A Brown, Judith Field, Alan G Baxter, Helmut Butzkueven

Life Science Alliance | LIFE SCIENCE ALLIANCE LLC | Published : 2020


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..

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Awarded by NHMRC

Awarded by Australian Research Council

Awarded by Multiple Sclerosis Research Australia

Awarded by Rebecca L Cooper Foundation

Awarded by Melbourne Brain Centre (National Health and Medical Research Council [NMHRC] center for Research Excellence)

Funding Acknowledgements

We thank all the people with MS and control persons who participated in this study. We also thank Lisa Taylor, Sandra Williams, and K-J Lazarus for their assistance with the collection of blood samples for this study. We would like to acknowledge the support and encouragement of this work provided by Mr Anton and Mrs Dulcie Christensen of Sarina, Queensland, Australia. Thank you to Johann Gagnon-Bartsch and Yujia Pan for providing details of the cross-normalization method. This work was supported by NHMRC Project Grants (#1032486) and project grants from the Australian Research Council (LP110100473) Multiple Sclerosis Research Australia (#15-025), the Lions Clubs of Australia (titled "New models of Multiple Sclerosis Susceptibility" and "Multiple Sclerosis Research Program"), and an equipment grant from the Rebecca L Cooper Foundation (#10027). MM Gresle was supported by fellowships from Multiple Sclerosis Research Australia (#14-069) and the Melbourne Brain Centre (National Health and Medical Research Council [NMHRC] center for Research Excellence grant 1001216). MA Jordan was supported by an NHMRC/MSRA Betty Cuthbert fellowship. M Bahlo was supported by an NHMRC Program Grant (GNT1054618) and an NHMRC Senior Research Fellowship (GNT1102971). This work was supported by the Victorian Government's Operational Infrastructure Support Program and the NHMRC Independent Research Institute Infrastructure Support Scheme (IRIISS). MA Brown is supported by an NHMRC Senior Principal Research Fellowship (#1024879). AG Baxter was supported by an NHMRC Fellowship (#1003118). J Field was supported by a Multiple Sclerosis Research Australia Fellowship. H Butzkueven is supported by an NHMRC practitioner fellowship (#1080518).