title: Blood RNA profiling in a large cohort of multiple sclerosis patients and healthy controls.
abstract: Multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system (CNS). It is characterized by the infiltration of autoreactive immune cells into the CNS, which target the myelin sheath, leading to the loss of neuronal function. Although it is accepted that MS is a multifactorial disorder with both genetic and environmental factors influencing its development and course, the molecular pathogenesis of MS has not yet been fully elucidated. Here, we studied the longitudinal gene expression profiles of whole-blood RNA from a cohort of 195 MS patients and 66 healthy controls. We analyzed these transcriptomes at both the individual transcript and the biological pathway level. We found 62 transcripts to be significantly up-regulated in MS patients; the expression of 11 of these genes was counter-regulated by interferon treatment, suggesting partial restoration of a 'healthy' gene expression profile. Global pathway analyses linked the proteasome and Wnt signaling to MS disease processes. Since genotypes from a subset of individuals were available, we were able to identify expression quantitative trait loci (eQTL), a number of which involved two genes of the MS gene signature. However, all these eQTL were also present in healthy controls. This study highlights the challenge posed by analyzing transcripts from whole blood and how these can be mitigated by using large, well-characterized cohorts of patients with longitudinal follow-up and multi-modality measurements.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Nickles
authors.forename: Hsuan P
authors.initials: HP
authors.lastname: Chen
authors.forename: Michael M
authors.initials: MM
authors.lastname: Li
authors.forename: Pouya
authors.initials: P
authors.lastname: Khankhanian
authors.forename: Lohith
authors.initials: L
authors.lastname: Madireddy
authors.forename: Stacy J
authors.initials: SJ
authors.lastname: Caillier
authors.forename: Adam
authors.initials: A
authors.lastname: Santaniello
authors.forename: Bruce A C
authors.initials: BA
authors.lastname: Cree
authors.forename: Daniel
authors.initials: D
authors.lastname: Pelletier
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hauser
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Oksenberg
authors.forename: Sergio E
authors.initials: SE
authors.lastname: Baranzini
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000235:genetics; D040641:Quantitative Trait Loci; D012313:RNA / Q000097:blood* / Q000235:genetics*; D059467:Transcriptome; D060449:Wnt Signaling Pathway / Q000235:genetics; D055815:Young Adult
chemical_list: D012313:RNA; D007372:Interferons; D046988:Proteasome Endopeptidase Complex