DNA from 1,600 ancient people and 400,000 UK Biobank participants reveals why MS is more common among northern Europeans: they are more closely related to the ancient people in which some of the genetic risk factors for the disease emerged.
Summary
Europeans who carry genes for an increased risk of multiple sclerosis (MS) tend to be more closely related to ancient herders that introduced domesticated animals to the continent millennia ago. They had evolved genes for a supercharged immune system – the same genes that are linked to an increased MS risk. The results, from an analysis of 400,000 UK Biobank participants’ DNA, could help scientists to develop new MS treatments.
Europeans that carry ‘multiple sclerosis (MS) genes’ are likely the descendants of animal herders who came from the steppes of eastern Europe and central Asia some 5,000 years ago, DNA data from UK Biobank participants have revealed.
The research addresses a long-standing mystery: why is MS more common among people from northern than from southern Europe? Understanding why some people have a higher genetic risk could help scientists to develop new MS treatments – and eventually bring us closer to a cure.
MS origins
MS is an autoimmune disease in which the immune system attacks the brain and nerves. There are some genetic traits that increase the risk of developing MS (although environment and lifestyle play an even bigger role). Researchers looked at DNA from more than 1,600 ancient skeletons, up to 11,000 years old, as well as that of more than 400,000 UK Biobank participants, tracing MS-related genes back in time.
Our lifestyle evolves much faster than our genetics. Now we have inherited an immune system that is better suited to survival in a different environment than the one we live in.
Professor Astrid Iversen, University of Oxford, UK
People in northern Europe, who more commonly carry MS-risk genes, tend to be more closely related to an ancient group called the Yamnaya. These herders arrived in northern Europe millennia ago, bringing with them domesticated animals as well as genetic traits for a supercharged immune system – the same genetic traits that are linked to an increased MS risk in modern people.
“Our lifestyle evolves much faster than our genetics,” says Astrid Iversen, one of the study’s leaders from the University of Oxford, UK. “Now we have inherited an immune system that is better suited to survival in a different environment than the one we live in.”
Europe’s first pastoralists
The Yamnaya people “lived a very extreme lifestyle”, Iversen says. “They were nomadic and lived very closely together with their animals. They consumed meat and dairy products and hardly any grains at all.” People were also constantly exposed to their animals’ pathogens.
We can see generation by generation how the genome is changing, which is incredible. I think Darwin would have been very excited.
Dr William Barrie, University of Cambridge, UK
It may have been in response to this onslaught of infectious diseases that the herders’ genes evolved rapidly. Genetic changes for a more active immune system would have allowed the Yamnaya people to better fight off infections and survive.
“We can see generation by generation how the genome is changing, which is incredible,” says study team member William Barrie from the University of Cambridge, UK. “I think Darwin would have been very excited.”
Around 5,000 years ago, the Yamnaya people moved into Europe, mixing with – and in some cases replacing – the hunters-gatherers and farmers who lived there. Modern Europeans are a mix of all three groups, though people from the northern parts have more Yamnaya ancestry.
A changing environment
Today, the pathogens we encounter are drastically different than what the Yamnaya people had to deal with. “We don’t have parasites anymore, so our pro-inflammatory response is, in many cases, likely a bit higher than we actually need to combat just bacteria and viruses,” Iversen explains. “If you constantly have heightened inflammation, it increases your risk of a cardiovascular diseases and autoimmune diseases.”
That MS has a heritable component has been known for a long time, says geneticist Samira Asgari from the Icahn School of Medicine at Mount Sinai, US, who is independent of the study team. “Seeing some aspects of human evolutionary history playing into that – the hypothesis is not new but having concrete evidence to support it – that was really cool.”
The exact reason why these genetic changes emerged in the Yamnaya people – whether it was related to protection from pathogens – needs further investigation, Asgari points out. “It makes sense, but it’s not necessarily backed by facts,” she says. “If this is a universal hypothesis, can we see it replicated in other populations, in other parts of the world?”
Gentler treatments
“I don’t think this particular study brings us closer to an MS cure,” Asgari says. “I do think that similar studies of understanding how our genome shapes our susceptibility to diseases, including MS, have and will bring us eventually closer to a cure.”
One of the things that’s difficult with chronic illnesses and living with them is the mystery of why you have them. I think anything to help explain why is a good thing.
Dr William Barrie, University of Cambridge, UK
Barrie hopes that this kind of research helps people to better understand their genetic predisposition for MS. “One of the things that’s difficult with chronic illnesses and living with them is the mystery of why you have them. I think anything to help explain why is a good thing.”
The results could even inspire researchers “to look into how parasite infections affect our immune responses, and if it’s possible to emulate some of these effects”, says Iversen. “That might be a more specific and gentle way to treat people.” There’s currently no cure for MS, and treatments that slow down its progression often fight the immune system with a blunt tool, Barrie says.
Without a resource such as UK Biobank the study wouldn’t have been possible, Iversen adds. “It’s really a huge gift that the [participants] have given the scientific community and society.”