Variant tied to severe MS may affect cognition in healthy adults

A genetic mutation associated with more severe disability in multiple sclerosis (MS) may also correlate with poorer cognitive performance in healthy people, a study reported.

People with MS, Parkinson’s disease, and dementia who carried the rs10191329A mutation showed similar trends of poorer cognition, though these didn’t reach statistical significance.

“Our results support the hypothesis that rs10191329A might affect multiple sclerosis outcomes by affecting brain health,” researchers wrote in the study, “The Multiple Sclerosis Severity Allele rs10191329A and Cognitive Function: A UK Biobank Study,” published in Molecular Genetics and Metabolism Reports.

Scientists don’t entirely understand the underlying causes of MS or its risk factors. However, certain gene mutations may increase the risk of developing the condition. Genetic variations can also influence the severity of MS symptoms and contribute to greater disability. Rs10191329A is one mutation, or genetic variant, associated with poorer disability outcomes.

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Mutation linked to brain health

Previous studies have found correlations between the Rs10191329A mutation and faster MS progression and greater brain tissue damage, suggesting the variant is detrimental to brain health.

This result led a team of researchers in the U.K. to hypothesize that rs10191329A may have implications beyond physical disability, and that it may also influence cognition in MS patients, people with other brain disorders, and healthy individuals.

To test this hypothesis, they used data from the U.K. Biobank, a large health resource that includes genetic information and other data for more than 500,000 volunteers recruited between 2006 and 2010.

The researchers identified nearly 400,000 biobank participants aged 40 to 69 with available data on the rs10191329A mutation. Of them, 2,026 people had MS, 1,466 had Parkinson’s, 2,337 had dementia, and more than 370,000 were healthy. Researchers also assessed people with migraine as a comparison group.

Among people with MS, there was a weak correlation between the number of rs10191329A copies and the frequency of disability claims, meaning people with two copies of the mutation were more likely to claim disability allowance than those with one copy, and this group had more disability claims than those without the mutation. However, this didn’t reach statistical significance.

The biobank includes results from several cognitive tests, including a reaction time test, a problem-solving and flexible thinking test (fluid intelligence), and a memory test. As expected, people with neurological disorders had worse cognitive performance than controls or those with migraine.

Additional analyses showed that controls with the rs10191329A mutation had worse results in all three tests compared with those without the mutation. The effect was subtle, but it was statistically significant.

These “weak but directionally consistent associations between rs10191329A and lower cognitive outcomes in healthy adults … are compatible with the hypothesis that this variant might influence MS severity through effects on brain health,” the researchers wrote.

Correlations in the MS, Parkinson’s, and dementia groups showed similar trends, but failed to reach statistical significance. Reaction times and fluid intelligence tended to be poorer in all three groups in patients carrying rs10191329A, and those with dementia carrying the variant also tended to have worse memory.

“Rs10191329A–a modifier of physical disability in MS–is associated with impaired cognitive outcomes in ~370,000 healthy adults,” the team wrote. “Despite limited power to detect analogous effects in MS or other neurological disorders, analyses suggested directionally concordant associations across health and disease.”

The researchers said more studies “in large disease-specific cohorts” are needed “to explore the impact of rs10191329^A on cognition in MS, other neurological disorders, and in health.”