How can genetics affect MS onset and progression? - MS Research Australia

How can genetics affect MS onset and progression?

Dr Yuan Zhou

Menzies Institute for Medical Research, TAS

| Causes and Prevention | Genetics | Fellowship | 2018 | Investigator Led Research |
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Summary

Over 100 genes have been linked to an increased risk of developing MS. We do not know the role of each individual gene, and which genes are involved in the progression and increase in disability associated with MS.

In this post-doctoral fellowship Dr Yuan Zhou aims to investigate some of these genes to determine what effect they have on the clinical course of MS. He plans to create a mathematical formula that includes genetic and environmental risk factors that can better predict the clinical course of MS in an individual person. This would enable the individual to better choose a therapy that would be most beneficial for them.

To achieve this, Dr Zhou will use data from around the world to determine the genetic factors that influence the onset and progression of MS. Part of this project will focus on genes located on the X chromosome. Females have two X chromosomes, and males have only one. By studying this chromosome, he may discover why more females than males develop MS. Along with understanding the clinical course of MS better, this work may also provide novel targets for future therapies.

 

Progress to Date

Through international collaborations, Dr Zhou has conducted a genome-wide association study (GWAS) analysis for Epstein Barr Virus (EBV) and Human Herpesvirus 6 (HHV-6), which are risk factors for the development of MS. This type of study involves searching all genes simultaneously for small variations that may be responsible for increasing the risk of developing MS. In preliminary findings, Dr Zhou has found multiple gene locations that may drive the immune response to these infections. These findings may help us to understand the way genes may be involved in driving the development and progression of MS.

Dr Zhou and his team are also looking into genetic variations that may predict the MS clinical course and have found a region which may increase the risk of MS progression. The team is currently investigating whether these variations cause changes in gene activity during MS progression. Dr Zhou has also found new genetic variations associated with lipid levels and body mass index (BMI) that are associated with disability progression in MS.

It is hoped that a risk model will be created that will take into account both genetic and environmental risk factors that will be able to make better predictions of an individual’s MS activity and provide guidance for treatment choices.

Dr Zhou has received the Ian Ballard Travel Award to travel to Harvard Medical School to determine why women are more predisposed to MS. He has also prepared and published several manuscripts in scientific journals.

Publications

Zhang Y, Zhou Y, van der Mei IAF Ausimmune/AusLong Investigators Group, et al (2019). Lipid-related genetic polymorphisms significantly modulate the association between lipids and disability progression in multiple sclerosis, J Neurol Neurosurg Psychiatry. 90:636-641

Afrasiabi A, Parnell GP, Fewings N, Schibeci SD, Basuki MA, Chandramohan R, Zhou Y, Taylor B, Brown DA, Swaminathan S, McKay FC, Stewart GJ, Booth DR (2019). Evidence from genome wide association studies implicates reduced control of Epstein-Barr virus infection in multiple sclerosis susceptibility. Genome Med. 11:26

Updated: 31 March 2019

Updated: 04 January, 2018

Investigator

  • Dr Yuan Zhou, Menzies Institute for Medical Research, TAS

Co-investigator

Grant Awarded

  • Postdoctoral Fellowship

Total Funding

  • $210,000

Duration

  • 3 years over 2018 - 2020

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