First genetic marker for MS severity identified

Scientists have discovered a genetic variant that correlates with a faster progression of multiple sclerosis (MS).

Previous studies have shown that the risk for MS lies in part in a dysfunction in the immune system. Treatment can slow down the diseases progression, but the researchers wrote that “these risk factors don’t explain why, ten years after diagnosis, some MS patients are in wheelchairs while others continue to run marathons.”

The study, which encompassed more than 22,000 people with MS, was the result of an international collaboration of over 70 worldwide institutions, led by researchers from the University of Cambridge in the UK, and UCSF in the US.

After sorting through seven million genetic variants, researchers identified one associated with faster MS progression. It sits between a gene involved in repairing damaged cells called DYSF, and one that helps to control viral infections, called ZNF638. Neither of these genes have a prior connection to MS, but researchers think that their proximity to the identified gene suggests they might be involved in MS progression.

“These genes are normally active within the brain and spinal cord, rather than the immune system,” said Dr Adil Harroud, lead author of the study and former postdoctoral researcher in the Baranzini Lab. “Our findings suggest that resilience and repair in the nervous system determine the course of MS progression and that we should focus on these parts of human biology for better therapies.”

The researchers also found that years in education and parental age were linked to MS severity, and that smoking worsened it. “Although it seems obvious that your brain’s resilience to injury would determine the severity of a disease like MS, this new study has pointed us towards the key processes that underlie this resilience,” they said.

Scientists will do more work to determine exactly how this variant affects DYSF, ZNF638, and the nervous system. They are also collecting an even larger set of DNA samples from people with MS, expecting to find other variants that contribute to long-term disability in MS.