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Genotype and Phenotype in Multiple Sclerosis—Potential for Disease Course Prediction?

  • Multiple Sclerosis and Related Disorders (J Graves, Section Editor)
  • Published:
Current Treatment Options in Neurology Aims and scope Submit manuscript

Abstract

Purpose of review

This review will examine the current evidence that genetic and/or epigenetic variation may influence the multiple sclerosis (MS) clinical course, phenotype, and measures of MS severity including disability progression and relapse rate.

Recent findings

There is little evidence that MS clinical phenotype is under significant genetic control. There is increasing evidence that there may be genetic determinants of the rate of disability progression. However, studies that can analyse disability progression and take into account all the confounding variables such as treatment, clinical characteristics, and environmental factors are by necessity longitudinal, relatively small, and generally of short duration, and thus do not lend themselves to the assessment of hundreds of thousands of genetic variables obtained from GWAS. Despite this, there is recent evidence to support the association of genetic loci with relapse rate.

Summary

Recent progress suggests that genetic variations could be associated with disease severity, but not MS clinical phenotype, but these findings are not definitive and await replication. Pooling of study results, application of other genomic techniques including epigenomics, and analysis of biomarkers of progression could functionally validate putative severity markers.

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Author information

Authors and Affiliations

  1. Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia

    Vilija G. Jokubaitis PhD & Helmut Butzkueven MBBS, PhD

  2. Department of Medicine and Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia

    Vilija G. Jokubaitis PhD & Helmut Butzkueven MBBS, PhD

  3. Department of Neurology, Royal Melbourne Hospital, Parkville, Australia

    Vilija G. Jokubaitis PhD & Helmut Butzkueven MBBS, PhD

  4. Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia

    Yuan Zhou PhD & Bruce V. Taylor MBBS, PhD

  5. Department of Neurology, Box Hill Hospital, Box Hill, Australia

    Helmut Butzkueven MBBS, PhD

  6. Department of Neurology, Royal Hobart Hospital, Hobart, Australia

    Bruce V. Taylor MBBS, PhD

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  1. Vilija G. Jokubaitis PhD
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  2. Yuan Zhou PhD
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  3. Helmut Butzkueven MBBS, PhD
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  4. Bruce V. Taylor MBBS, PhD
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Correspondence to Bruce V. Taylor MBBS, PhD.

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Conflict of Interest

Vilija G. Jokubaitis, Yuan Zhou, and Bruce V. Taylor declare no conflict of interest.

Helmut Butzkueven is on the Australian advisory board and Global Advisory boards for Novartis, Biogen, Merck, and Teva, and is a consultant for Novartis (Progressive MS consultancy) and Oxford Pharmagenesis (MS Brain Health Steering Committee). Dr. Butzkueven reports research grants from Biogen and Novartis and lecture fees paid to him from Biogen. Dr. Butzkueven has received payment for the development of educational presentations for Biogen (MS Atlas Meetings), Novartis (National MS workshop), and Merck (Global Registries workshop).

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Multiple Sclerosis and Related Disorders

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Jokubaitis, V.G., Zhou, Y., Butzkueven, H. et al. Genotype and Phenotype in Multiple Sclerosis—Potential for Disease Course Prediction?. Curr Treat Options Neurol 20, 18 (2018). https://doi.org/10.1007/s11940-018-0505-6

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  • DOI: https://doi.org/10.1007/s11940-018-0505-6

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