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MS Gene Discovery

11 January 2024

An international team of scientists has discovered that the genes which protected our ancestors from animal diseases now raise the risk of multiple sclerosis (MS) in today's humans. The researchers have called their discovery "a quantum leap" in understanding the evolution of the disease, and say it could change opinions on what causes MS, and have an impact on the way it is treated. 

There are about twice as many cases of MS per 100,000 people in north-western Europe, including the UK and Scandinavia, compared with southern Europe. Researchers from the universities of Cambridge, Copenhagen and Oxford have spent more than 10 years delving into archaeology to investigate why.

Their research, recently published in the journal Nature, discovered that genes which increase the risk of MS entered into north-western Europe about 5,000 years ago via a massive migration of cattle herders called Yamnaya. They came from western Russia, Ukraine and Kazhakstan, and moved west into Europe.

The findings "astounded us all", said Dr William Barrie, paper co-author and expert in computational analysis of ancient DNA at the University of Cambridge. At the time, the gene variants carried by the herding people were an advantage, helping to protect them against diseases in their sheep and cattle. Nowadays, however, with modern lifestyles, diets and better hygiene, these gene variants have taken on a different role, causing a higher risk of developing certain diseases, such as MS.

The research project extracted genetic information from ancient human remains found in Europe and Western Asia, and compared it with the genes of hundreds of thousands of people living in the UK today. Prof Lars Fugger, paper co-author and MS doctor at the John Radcliffe Hospital in Oxford, says the discovery helps demystify the disease: "MS is not caused by mutations - it's driven by normal genes to protect us against pathogens," he explains.

Vaccinations, antibiotics and higher standards of hygiene have changed the disease landscape completely - many diseases have disappeared and people are living decades longer. The researchers say modern immune systems may now be more susceptible to autoimmune diseases, like MS, where the immune system attacks the body rather than protecting it.

Drugs currently used to treat MS target the body's immune system, but the downside is the risk of suppressing it so much that patients struggle to fight off infections. When treating it, we are up against evolutionary forces, Prof Fugger says: "We need to find the sweet spot where there is a balance with the immune system, rather than wiping it out."

Researchers believe that the Yamnaya herders could also be responsible for north-western Europeans being taller than southern Europeans. And while northern Europeans carry more genetic risk for MS, southern Europeans are more likely to develop bipolar disorder, and eastern Europeans are more likely to have Alzheimer's disease and type 2 diabetes.

A bank of DNA from 5,000 ancient humans, kept in museum collections across many countries, has now been set up to help future research. The team plans to look for other diseases in ancient DNA and follow them back in time, which could reveal more about the origins of conditions such as autism, ADHD, bipolar disorder and depression.

Read the full research paper >

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