The genetic reason for high rates of MS in Northern Europe

First up this week, let’s look at a big story in the genetics sphere, and what might be some of the deeper questions being asked by geneticists. It’s time to venture back down into Cambridge and link up with one of my genetics gurus, Shivani Shukla.

Will - Lovely to be back in Cambridge. Shivani, you're flying solo this month. How do you feel?

Shivani - Very exciting. Thank you for having me.

Will - How does it feel to know that 99.9% of all the genetic knowledge in this room is currently in your head?

Shivani - Are you sure It's not a hundred percent <laugh>

Will - Well, I guess we'll find out. Anyway, let's jump into the story. It's a seemingly huge story and has generated not one but four papers in the journal Nature. Spearheaded by several universities including the University of Copenhagen, but also the University of Cambridge, where we are sitting right now. Researchers have created the world's largest ancient human gene bank by analysing the bones and teeth of almost 5,000 humans who lived across Western Europe and Asia up to 34,000 years ago. The new study has found that genes that significantly increase a person's risk of developing multiple sclerosis were introduced into Northwestern Europe around 5,000 years ago by sheep and cattle herders migrating from the East. Shivani, first and foremost, before we get into the genetic side of things, what is multiple sclerosis?

Shivani - Multiple sclerosis is an autoimmune disorder, which means your immune system is overactive and essentially starts attacking things that it shouldn't. So in this case, it's the myelin sheath that's found on the outside of nerves and once you attack that, the nerves don't function properly. You get things like motor disorders, sensory disorders, and it can have quite an impact on someone's quality of life.

Will - Stuff like this is definitely worth then finding out where something like multiple sclerosis came from. And this is seemingly what they've done. They've said here in the paper, that they've taken samples of bones and teeth from 5,000 individuals. But then how do you go from that to a genetic map of the past that you can use to track diseases?

Shivani - There were already a lot of specimens sitting in museums across Europe and beyond the DNA of those 5,000 specimens were then sampled to create the first of its kind actually, which is an ancient gene bank. And then to translate that to seeing how that impacts multiple sclerosis in the present day population, they took data from the UK Biobank. So then you just compare and contrast the two using statistics and that allows you to trace backwards and forwards.

Will - And now that we found this seemingly this nexus point of about 5,000 years ago where multiple sclerosis has been introduced into Northwestern Europe, and you've said that it's a bad thing in terms of being a neurodegenerative disease, but the paper seems to allude to the fact that it wasn't necessarily bad for the people that had this genetic marker at that time.

Shivani - That's true. And I think it's important to point out that biogenetic marker, we are not saying that multiple sclerosis was advantageous to those people. What actually happened was the genes that code for advantageous things 5,000 years ago, which in this case was protection against certain diseases, were actually pleiotropic. So that one gene coded for multiple proteins or multiple traits and it just so happened that that also conferred a higher probability to get to multiple sclerosis.

Will - I hate to use words like ‘trade off’ because it implies choice or sentience, but the fact that it is seemingly worth risking MS to be able to stave off these diseases.

Shivani - I suppose so, and you have to think the lifestyles of the people at the time who were raising cattle probably didn't live much beyond thirties anyways, so they didn't really run into the troubles of multiple sclerosis later on. They were just trying to stay alive and eat and live. So in this study they also found that hunter gatherers there were many genes that conferred protection against similar diseases as these cattle herds. But actually even more specific diseases like viral haemorrhagic fever and mosquito carried infections, but those genes gave them a higher risk of things like rheumatoid arthritis, which is another autoimmune condition. So that's another example of that gene was protective at that time and was probably positively selected for, and now we are not staving off viral haemorrhagic fever, but we have the remnants for that gene and unfortunately that gives those people or descendants of those people a higher risk of autoimmune conditions.

Will - I suppose then that kind of leads us to the present day and knowing this and knowing what we know now, is there anything we can do with this in terms of treatment?

Shivani - I think it's an interesting way of looking at a disease because you can kind of think about the advantages of a disease. And that's true for things like sickle cell anaemia, which disproportionately affects African-American population and it's advantageous to protect them against malaria. So when you start to see things from a different perspective, perhaps that can kind of guide the pathways in which you take. And perhaps those inflammatory markers or those chemicals that are associated with fighting off pathogens might be the ones that we want to start targeting for MS because there's an underlying link, which perhaps we didn't know about before.

Will - As with every good scientific paper, they are always going about what they want to achieve in the future. And their plans are to look at the genetic markers of stuff like ADHD, schizophrenia, bipolar disorder. What would you personally be most interested in finding the origins? If you could pick any neurodegenerative disease, what would be the most interesting you think to find the origins of?

Shivani - That's a very interesting one. <laugh>. I think for things like ms, because we know it's autoimmune, you'd think there's an immune advantage of it at some point, so that's less surprising. But perhaps Parkinson's, which is a movement disorder and degeneration of the dopamine neurons over time lead to quite shaky movements and the symptoms we associate. And it makes me wonder what could be the advantage of a movement disorder because that's less obvious than something immune related. And it's really hard to hypothesise, do you have any ideas about something that controls movement might be advantageous. And especially its coordinated movements.

Will - Unless it is simply tied to something else that is advantageous and it was deemed worth it then that you could therefore survive long enough to procreate and, whoopsie, you got Parkinson's, but at the end of the day you still managed to reproduce. It's all a mystery. And I for one, am very interested to see where this paper goes in future.