Making MS genetics more representative


Although no one understands exactly why some people get MS, it is clear that both your genetics and your environment play a role. There is no such thing as a single gene that causes MS – if this existed, this large study from 2005 would have probably found it. Instead, changes in hundreds or maybe even thousands of genes are likely to incrementally affect your susceptibility to MS, each by an individually-small amount. It is probable that some individuals are more or less susceptible to the disease due to their genetics, but that a further ‘hit’ is required to cause the disease. The interplay between genetics and environmental hits in the early stages of MS are not well-understood at all.

Amazing collaborative efforts by the International MS Genetics Consortium (IMSGC) have found 233 hotspots in the genome where variation can increase your risk of MS. However, with a couple of exceptions, the mechanisms linking these gene hotspots to MS remain elusive. Understanding how these genes increase the risk of MS might lead to a better understanding of the pathways involved. This understanding could reveal better drug targets for treating, or perhaps even preventing MS in the distant future.

Most efforts to understand the genetics of MS have focussed on individuals with European ancestry. As a research community, it’s incumbent on us to ensure that we broaden participation in MS genetics studies to include people from all ancestral backgrounds. There are strong arguments for doing this from a purely ethical standpoint – encouraging representative research ensures that any downstream benefits from this kind of research are enjoyed by everyone with MS equally. Failure to include individuals with non-European ancestral backgrounds in MS genetics research – and in fact medical research more generally – risks exacerbating healthcare inequalities by limiting the generalisability of these insights.

But in addition to the ethical case, there is a strong scientific case for improving the representativeness of MS genetics research.

Each of us has about 3 billion letters – one of ‘A’, ‘C’, ‘T’ or ‘G’ – in our genome. Of these letters, only about 10% actually differ at all between individuals. These sites – where individuals may differ in which letter they have – are called ‘variants’. People from different ancestral backgrounds have slightly different genetic variants from each other. This ancestral diversity stems from a massive migration event out of Africa ~60,000 years ago. As well as having slightly different sets of variable letters, different ancestral groups also have different correlations between letters: an ‘A’ at one position might always be inherited with a ‘T’ at a nearby position in European populations, but not in South Asian populations.

As a result, studying MS in different ancestral populations has several advantages. It may uncover new risk variants within known genes (or even within new genes) because these variants are either invariant in European populations or too rare to detect. It may also help to clarify how changes in the genome lead to MS, as information from different populations can be used to ‘triangulate’ the signal. A great example of these advantages comes from a genetic study of MS risk in the Sardianian population, which is genetically rather distant from mainland European populations. This study uncovered a new variant associated with MS risk, and this led to a better understanding of how the B cell survival factor – BAFF – plays a critical role in MS. This finding was possible because the variant discovered was too rare in English, Italian mainland, or Swedish cohorts to detect.

There are many other scientific arguments for studying MS genetics in diverse ancestral groups which I will explore in future posts. I hope I’ve convinced you that doing this work has the potential to benefit everyone with MS, including people from European backgrounds.

We’re trying to understand how genes contribute to MS risk with an emphasis on people from non-European backgrounds. Our study – the ADAMS study – launched last month and is recruiting right now. If you have MS and you identify as having non-European ancestry, we need your help. You can sign up from your home via the website. Taking part involves 2 steps:

  1. Answering a ~15 minute questionnaire on the website, and
  2. Sending us a saliva sample in the post (we’ll send you the kit and all the packaging)

If you’re interested please get in touch with us. You can

  • Visit the website:
  • Follow us on twitter
  • Watch a podcast by Roxy Murray, a member of our participant steering group, and by Dom Shadbolt from the (both embedded below)
  • Read more on the MS Society website
  • Email the team at

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Leave a Reply to Tony Fonda Cancel reply

  • This is exactly me and I am more than willing to help, but I signed a pledge with me, mys of and I a few years ago where I will only participate in MS research if I the lead researcher agrees to pay me back with my own results.
    In other words, I will give you saliva if you agree to hand me back my data points.

    • Thanks Tony – we’re allowed to feed back summary results for everyone who takes part and we’ll tell you if we find anything unexpected which you need to know about for medical reasons (e.g. changes in your genes which make you very likely to have dangerously high cholesterol). Beyond that we don’t have ethical approval to feed back your individual genetic profile. The reason for this is that this kind of information isn’t interpretable in a meaningful way – the vast majority of variants we test have unknown effects, and so our view is that it’s irresponsible to feed back information which cannot help you. Would be very happy to talk over phone if you’re interested – please drop me a line at if you’d like to discuss

      Take care

      • Thanks Ben,

        I think it is unethical for you to determine what is ethical, keeping in mind that many of you are still OK running trials against placebos or platform therapies.

        My ethics say I and only I decide what is right for me and you owe me my data.

        I encourage all MSers to ask for the same. That right is ours.

        To y

        • Hi Tony, I understand where you’re coming from. The study has been scrutinised by an NHS Research Ethics Committee whose job it is to make sure that studies are designed in an ethical way and keep participants’ interests at heart.

          Obviously there’s no compulsion on you or anyone else to participate if it’s not for you.

          If you feel strongly about us feeding back certain types of data to individuals this is something we could explore and I would be keen to take forward. We have a fantastic steering committee who I’m sure would be interested to discuss the proposal. Please email me at if you want to discuss.

          • I would rather keep that conversation in the public domain if OK with you.
            The question is how much do I, as an individual is worth to your study? Or us as a collective? How many research subject sit on ethics committees?

            People should stop being taken for granted. You know better and this blog should lead the way.

            There is no compulsion on you to come back with a better/improved offer, or be an agent of change in any shape or form. But I will support you if you decided to do so.


  • Is this for people within the UK or can other countries also join? I would be a great addition if I may say as I am biracial and far from inbred (I hope)

    • Thanks Steve – at the moment our ethics only covers the UK but we are always interested in how to extend the study further afield. If you don’t mind dropping me a line at with some more info I’ll see what I can do

  • Very well written and understandable, interesting in my “book”. Can’t help you, though. (64 yrs, MS 35 yrs, European background in US, 🙁 Studying genetics is merely finding out the truth which is what is great about it.

  • The ethos behind studies seems to be looking for causative genes, whereas I think this type of study should be looking for protective genetics. Once found, there are new gene therapies that could be applied to these loci. The Atara T-cell modification is an example of this ethos and we should be looking for more protective potential therapeutic targets, rather than looking a causative gene that probably doesn’t exist.

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