Genotype-Phenotype Correlations in Multiple Sclerosis

Research Opportunity
Project Status
Medicine and Radiology
Royal Melbourne Hospital
Supervisor Email Number Webpage
Dr Vilija Jokubaitis Personal web page
Prof Helmut Butzkueven +61 3 93427061 Personal web page

Project Details

Synopsis MS is a complex polygenic and environmentally determined disease. MS risk has been linked to over 200 single nucleotide polymorphisms (SNPs), each with average increased odds of developing MS within the range of 1.1-1.3. To date, the only replicated genetic modifier of any MS phenotype the main risk allele, HLA-DRB1*1501, which confers reduced age of onset. The best evidence to-date for a genetic basis underlying phenotypic outcomes comes from a small number of cross-sectional genome-wide association studies a priori dedicated to a search for severity signals. These studies have had modest success in cumulatively identifying 109 putative modulators disease outcome. Critically however, a functional dichotomy between genes involved in susceptibility and those that regulate severity has been reported, the latter having an over-representation of signals related to CNS and embryonic development, and cellular respiration. Therefore, strong preliminary evidence exists that genetic variation does influence phenotypic outcomes, however this remains to be validated.

This PhD project will utilise genetic data that is linked to a global observational cohort to identify genotype-phenotype correlations with

  1. clinical phenotypes
  2. MRI phenotypes.

Further, genetic variants will be incorporated into prognostic models to determine whether they exert an independent effect on disease outcomes.

Outcomes and impact

The identification of genetic predictors of MS phenotype will have a significant impact on MS management, with the capacity for rapid translation in to clinical practice through the development of a genetic test of disease outcome. It will inform risk/benefit decision-making when selecting appropriate therapies for individuals, and thus maximise quality of life and reduce economic burden. Biologically, success in genetic analyses will provide insight into the molecular mechanisms of MS progression.

Research Environment

The proposed project will be undertaken using the MSBase Registry, an international, prospective, observational MS cohort study. It currently contains over 50,000 longitudinal patient records, with over 230,000-patient years of follow-up. Within the MSBase observational cohort study, we have formed a special interest group to examine genetic predictors of disease outcome. This group comprises 11 centres that have the capacity to undertake genetic studies. Here, our cohort comprises 8,574 patients, with 60,000 patient-years of follow-up with visits occurring on average every 6 months. In addition, we are also actively collaborating with the Swedish National Registry/MultipleMS (EU2020) on this project.

Faculty Research Themes


School Research Themes

Neuroscience & Psychiatry

Research Opportunities

Graduate Research Students who are interested in joining this project will need to consider their elegibility as well as other Graduate Research requirements before contacting the supervisor of this research

View application process

Key Contact

For further information about this research, please contact a supervisor.


Medicine and Radiology

Research Group / Unit / Centre

MS Biology, Genomics and Prognostics Group

Research Node

Royal Melbourne Hospital

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