MS genetic risk factors are largely shared across South Asian, African, and European ancestries

Almost everything we know about the genetics of multiple sclerosis comes from studying people of White European descent. That is a problem, because MS affects more than two million people worldwide across all ancestral backgrounds, and the genetic risk architecture may not be uniform. A new study, one of the most ancestrally diverse MS genetic analyses conducted in the UK, provides both reassurance and a warning on that front.

The reassurance: the core genetic drivers of MS risk appear to be largely shared across populations. The warning: studies that only include Europeans miss variants that matter.

3,000 patients, three ancestries

The study, published in Neurology and led by Queen Mary University of London, analyzed genetic data from more than 3,000 people with MS and over 27,000 controls. Participants were drawn from the ADAMS Project, which specifically recruits people with MS from diverse backgrounds, and from the UK Biobank. The analysis included people of South Asian, African, and European ancestry.

The researchers focused first on the major histocompatibility complex (MHC) region, a section of the genome critical to immune function and long established as a major driver of MS risk. They found that MHC variants were strongly associated with MS across all three ancestry groups -- suggesting that the same fundamental immune mechanisms underlie the disease regardless of genetic background.

A protective variant hiding in plain sight

But the shared architecture was not the whole story. The researchers identified a genetic variant that appears to reduce MS risk and is relatively common in people of South Asian ancestry but rare in people of European ancestry. Because this variant is uncommon in Europeans, it would likely never be detected in studies that only include European populations.

This is not a minor methodological footnote. If a protective variant exists primarily in one population and genetic studies systematically exclude that population, the variant remains invisible -- and so does any therapeutic insight it might provide.

"MS genetics has, until now, been overwhelmingly based on people of European ancestry," said Ruth Dobson, Professor of Clinical Neurology at Queen Mary and lead author. "This study shows that while many of the biological pathways driving MS are shared, leaving large parts of the global population out of research limits our understanding of the disease."

Shared pathways, varying strengths

The study also examined whether genetic variants previously identified in European populations appear in other ancestry groups. Most did. While the strength of individual effects varied between populations, the overall pattern suggests that MS is driven by shared underlying immune and biological mechanisms rather than being a fundamentally different disease in different ancestral groups.

This finding has practical implications for genetic risk prediction tools and potential treatments developed from European-focused data. If the same pathways are involved, such tools and treatments are more likely to be broadly relevant. But the varying effect sizes mean they may not perform equally well across populations without calibration.

Disparities beyond genetics

Previous research has documented stark racial disparities in MS outcomes. People from Black ethnic backgrounds often experience more severe disability and worse disease trajectories than White patients. Genetics alone does not explain these disparities -- they also reflect differences in access to care, diagnostic timing, socioeconomic factors, and potentially environmental exposures.

But the underrepresentation of non-European populations in genetic research compounds these problems. MS may be under-recognized in some communities, diagnosed later, or assessed using tools developed and validated in different populations. Co-author Benjamin Jacobs, a Clinical Lecturer in Neurology at Queen Mary, noted that "when studies only include one ancestral group, they miss important insights. By broadening participation, we can sharpen our understanding of MS, find risk factors that would otherwise stay hidden and build prediction tools that work for everyone."

Study scope and limitations

While this is one of the most diverse MS genetic studies to date, the non-European sample sizes remain small compared to the European cohorts that dominate the field. The statistical power to detect ancestry-specific variants is correspondingly limited. Larger, dedicated studies in South Asian and African populations would be needed to fully characterize the genetic risk landscape in these groups.

The study was funded by the National Multiple Sclerosis Society and Barts Charity.