An international study of more than 20,000 people with MS identified gene variants linked to faster MS progression. The study also confirmed the role of tobacco smoke to worsening MS, and educational attainment to less severe outcomes. Unlike previous studies reporting genetic variants linked to MS risk being predominantly tied to immunological function, these variants are in pathways related to nervous system function. The study provides new clues to developing therapies to stop MS and more evidence for actions to take that may reduce disease progression.
Background: Accelerating new, life-changing treatments for people with progressive MS requires new insights and knowledge into the causes of progression. By determining what triggers MS progression, researchers will be better prepared to focus their efforts on developing breakthroughs to slow, prevent, and ultimately, reverse disability. The
International MS Genetics Consortium (IMSGC) had previously published the largest MS genetics study to date, identifying 233 genetic variants associated with susceptibility to developing MS and are primarily in pathways relating to immune functions. But up to now, no genetic variants have been linked to how severe the disease will be in individuals.
Recently the IMSGC has been seeking a genetic explanation for progressive courses of MS, with funding from the National MS Society. For this effort, the group joined with the international
MultipleMS Consortium, which aims to develop novel personalized medicine approaches for people living with MS.
The Study: This international group recruited 12,584 people with MS through 21 centers from North America, Europe, and Australia. They used blood samples to conduct a genome-wide association study – meaning that they surveyed the entire human genome – and linked genetic variants with an MS severity score, as well as tissue damage observed on imaging scans and several known risk factors for speeding up MS worsening such as smoking. The results were further confirmed in another 9,805 people with MS.
- The team found that one variant (called rs10191329) was significantly associated with shortening the time until the use of a walking aid was needed, and also with increased tissue damage in the brain. They found a weaker link to another gene variant (called rs149097173) that shortened the time to needing a walking aid. Further study showed evidence that confirmed that smoking was associated with worsening MS progression, and educational attainment had a protective effect.
Why does this matter?
- Identifying genetic links to MS progression provides new clues to developing therapies to stop progression in its tracks. The gene variants pinpointed in this study are in biological pathways linked to nerve functions and suggest several opportunities for exploring how MS gets worse and how to make it better.
- The links to smoking and educational attainment warrant attention because these are factors that can be modified. For example, there are ways to stop unhealthy habits and address issues that make school days harder.
Learn More…
Watch a webcast from the International Progressive MS Alliance
“Developing Treatments to End MS Progression: Recent Advances and Promising Research”
Learn more about progressive MS in
“Ask an MS Expert: Progressive MS”
“Locus for severity implicates CNS resilience in progression of multiple sclerosis” by Adil Harroud, Sergio Baranzini, and the International MS Genetics Consortium and MultipleMS Consortium is published in
Nature (published online June 28, 2023).