Skip to main content
Premium Trial:

Request an Annual Quote

Multiple Sclerosis Risk Score Provides Clues to Treating Vision Loss Condition

NEW YORK – New research suggests it may be possible to more accurately predict multiple sclerosis (MS) risk by combining a polygenic risk score for the condition with information on a vision loss condition that tends to overlap with MS and other inflammatory conditions.

"This pioneering investigation establishes a link between an individual's combined genetic susceptibility … and the subsequent risk of MS development in those experiencing an initial episode of undifferentiated [optic neuritis]," co-senior authors Tasanee Braithwaite, a consultant neuro-ophthalmologist with King's College London and Guy's and St Thomas' Hospitals, and Richard Oram, at the University of Exeter and Royal Devon University Healthcare NHS Foundation Trust, and their colleagues wrote in Nature Communications on Wednesday.

Such a distinction is expected to be particularly important since optic neuritis cases found in individuals with MS often resolve over time, while the presence of optic neuritis in individuals at low risk of MS typically benefit from rapid corticosteroid treatment.

"There is an unmet clinical need for a tool to improve acute risk stratification, differentiating those at low future MS risk who may benefit from urgent corticosteroids, from those at high future MS risk who may benefit from earlier disease-modifying therapy to reduce long-term neurological disability," the authors explained.

For their study, researchers from King's College London, the University of Exeter, and elsewhere used directly genotyped variants from more than 483,500 unrelated UK Biobank participants, together with imputed variant profiles, to assess genetic features found in 2,103 individuals with MS alone, 421 optic neuritis cases, and 266 individuals with both MS and optic neuritis, comparing them to one another and to 480,690 unaffected control individuals.

"Previous genome-wide association studies, led by members of the International Multiple Sclerosis Genetics Consortium, established that there are at least 200 genetic loci contributing to MS genetic risk," Braithwaite explained in an email. "Our study built on this foundation, to explore whether we could better predict which patients with a first episode of optic neuritis might develop MS in the future, by adding genetic information to demographic and clinical variables."

Among other results, the team found that the ability to predict future MS development in individuals with optic neuritis could be improved by considering a 317-variant MS genetic risk score (MS-GRS) in combination with established demographic measurements such as age and sex.

"[O]ur study unveils the potential of a composite model that integrates MS-GRS with age at [optic neuritis] onset and sex, offering a means to stratify patients based on their likelihood of a future MS diagnosis," the authors reported, "thus providing valuable insights for clinical management decisions."

While the incidence of MS was estimated at 4 percent in individuals with optic neuritis who fell in the lowest-risk category with the MS-GRS, for example, the researchers reported that MS rates rose to around 41 percent in optic neuritis patients from the highest-risk group on the MS-GRS model — results that were backed up by their subsequent analyses on data from the FinnGen and Geisinger studies.

"This research indicates that adding genetic information to demographic and clinical data could improve risk stratification at first presentation with optic neuritis, better-identifying patients at high MS risk," Braithwaite explained, noting that the team anticipates exploring the findings further in a prospective clinical setting.

"This could pave the way for more targeted investigation and management of optic neuritis in the acute setting," she added, "both for patients identified to be at high MS risk — who might benefit from earlier referral to MS services to consider disease modifying therapy, and for patients at low MS risk — who might need urgent treatment to prevent permanent sight loss."