August 13, 2019  Print

A new study published in the prestigious Nature Communications journal shows that a data-driven approach could help fast-track research into multiple sclerosis (MS) risk genes. It could also improve our understanding of how MS develops and progresses.

Professor David Booth was a leading contributor to the study.
The study was conducted by the International Multiple Sclerosis Genetics Consortium, a global collaboration between MS researchers. A team from The Westmead Institute for Medical Research (WIMR) plays a key role in this consortium. 

One of the leading contributors to this study is Professor David Booth, head of the Immunogenetics Group at WIMR. He says the results demonstrate that, by integrating information about gene variants obtained from Genome-Wide Association Studies (GWAS) with existing information about gene regulation and protein interactions, researchers have an accurate way to predict why and how a disease will develop, and how it might progress.

Professor Booth said, “GWAS is a relatively new way for scientists to search the genome (the complete set of genes in a cell) for gene variations that occur more frequently in people who have a particular disease. It helps us to pinpoint genes that might contribute to an increased risk of developing that disease.”

This study looked primarily at MS and has demonstrated statistically significant results relating to genes and pathways that are known to be involved in the development and progression of MS.
Multiple sclerosis is a condition of the central nervous system that affects the nerve impulses in the brain, spinal cord and optic nerves.  According to MS Australia, more than 25,600 Australians are currently living with MS.[1]

Previous research published by the Multiple Sclerosis Genetics Consortium revealed there is a total of 223 significant genome-wide associations, and an additional 416 variants that are potentially related to MS.

Professor Booth says, “This most recent study has developed a framework to interpret these associations, specifically in the context of how proteins work together in these cells.
“The results generated by this most recent study are consistent with previous research findings that show MS risk is driven by long-term changes to cellular pathways, primarily in a type of white blood cell called monocytes, but also in B and T immune cells.”

Professor Booth says that the benefit of using this data-driven approach is that it will help to fast track research into how risk genes can affect immune responses and MS. There is now an enormous amount of research on how genes are turned on and off in different immune cells, and the effects of the genetic variants on this.  This study devised a computational approach to collate all that research to find the answers to questions, including which particular immune cells are affected by the genes controlling risk of developing MS?  What is the effect in these immune cells of the genetic variant increasing risk of MS? In this way, we can develop strategies to stop the processes that lead to MS, and halt the disease. 

“This sort of study requires huge data input, and contributions from many scientists. This is why the work of the IMSGC collaboration is so valuable."

This study was supported by funding from many international organisations.  The full research paper, including a list of funding bodies can be found here.

Professor David Booth is affiliated with Sydney University and The Westmead Institute for Medical Research.