Article Text

Systematic review of genome-wide expression studies in multiple sclerosis
  1. A K Kemppinen1,2,3,
  2. J Kaprio1,4,5,
  3. A Palotie1,6,7,8,
  4. J Saarela1,9,10
  1. 1Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
  2. 2Helsinki Biomedical Graduate School, University of Helsinki, Helsinki, Finland
  3. 3Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
  4. 4Department of Public Health, University of Helsinki, Helsinki, Finland
  5. 5Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland
  6. 6Program in Medical and Population Genetics and Genetic Analysis Platform, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
  7. 7Department of Medical Genetics, University of Helsinki, Helsinki, Finland
  8. 8Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK
  9. 9Department of Gynecology and Pediatrics, Helsinki University Central Hospital, Helsinki, Finland
  10. 10Department of Child Psychiatry, Helsinki University Central Hospital, Helsinki, Finland
  1. Correspondence to Anu Kemppinen; ak635{at}


Background Although recent genome-wide association studies have identified several genetic variants contributing to the complex aetiology of multiple sclerosis (MS), expression and functional studies are required to further understand its molecular basis.

Objectives To identify genes and pathways with differential expression in MS.

Design The authors conducted a systematic review of seven microarray studies, in which expression in immune cells was compared between MS patients and controls. These studies include a previously unpublished study, which is described here in detail.

Results and conclusion Although in general the overlap between studies was poor, 229 genes were found to be differentially expressed in MS in at least two studies, of which 11 were in three studies and HSPA1A in four studies. After excluding the authors' unpublished experiment which may have been affected by certain confounding factors and inclusion of treated subjects, 135 genes were identified in at least two studies. The differentially expressed genes were significantly associated with several immunological pathways, including interleukin (IL)-4, IL-6, IL-17 and glucocorticoid receptor signalling pathways. 15 of the 229 loci have shown some association with MS in published genome-wide association studies (p<0.0001), including three loci with confirmed MS risk variants.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: and

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  • To cite: Kemppinen AK, Kaprio J, Palotie A, et al. Systematic review of genome-wide expression studies in multiple sclerosis. BMJ Open 2011;1:e000053. doi:10.1136/bmjopen-2011-000053

  • Funding This work was supported by the Sigrid Juselius Foundation, Helsinki University Central Hospital, the Academy of Finland Centre of Excellence in Complex Disease Genetics, the Neuropromise EU project (grant number LSHM-CT-2005-018637) and the Helsinki Biomedical Graduate School.

  • Competing interests None.

  • Ethics approval The study was approved by the Committee on Ethics of the Central Hospital of Central Finland and by the Helsinki University Hospital Ethical Committee of Ophthalmology, Otorhinolaryngology, Neurology and Neurosurgery (permit 192/E9/02) for FITSA and patient samples, respectively.

  • Contributors Sample handling and laboratory work: AK. Data analyses: AK. Manuscript writing: AK, JK, AP, JS. Approval of final manuscript: AK, JK, AP, JS.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement The previously unpublished microarray expression dataset will be available through Gene Expression Omnibus (GSE21942).

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