Long-term MS outcomes can vary widely between people with relapse-onset MS. The aim of Dr Jokubaitis’ fellowship was to determine whether a person’s DNA has an impact on whether they are likely to develop mild, moderate or severe MS.
Using data from an international MS clinical outcomes register called MSBase, the team identified people with relapse-onset MS whose disease was mild, severe, and those in between. In collaboration with scientists and neurologists across Australia, the Czech Republic, and Spain, people were invited to donate DNA so that the research team could look for a link between their genetic make-up and how their MS progressed.
First Dr Jokubaitis sought to repeat already published studies that identified 117 genetic variations that might be associated with MS severity, but were inconclusive. Of these, only one genetic variation was identified that impacts the age at which a person develops MS, but not MS severity.
Next, a series of experiments was conducted looking for new links between DNA variations and MS severity. In this study of 1,813 people, the team found no new associations between over 5 million genetic variations and long-term MS outcomes. They also split the study group to look at genetic variations only in men, or only in women. When looking at the genders individually, they found two new DNA variations associated with MS outcomes, one in men, and one in women. However, these associations were very not strong, and therefore future studies still need to confirm these findings to answer the question more definitively.
What does this tell us? It tells us that MS outcomes are not under strong genetic control. As with MS risk, it is likely that many genetic variations may contribute small amounts to a person’s outcomes, but there is no “smoking gun” to explain the whole process. Furthermore, it tells us that MS outcomes are modifiable, and that your genes are not your fate, there are other factors at play as well. It tells us that outcomes can be modified by appropriate use of MS therapies, and also likely by various environmental factors.
The next exciting areas for research in this field include a project underway with Professor Rodney Scott, examining how the body switches genes on and off, or “epigenetics”, and how this affects MS severity. Furthermore, the effect of genetics on MS severity may be more so determined by how genes affect response to MS therapies, and these investigations are underway in Dr Jokubaitis’ laboratory.
Updated: 29 April 2021
Updated: 11 February, 2017