It’s not all in the Genes! Elements of MS are preventable by changing the environment

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Multiple sclerosis among first- and second-generation immigrants in Denmark: a population-based cohort study. Munk Nielsen N, Corn G, Frisch M, Stenager E, Koch-Henriksen N, Wohlfahrt J, Magyari M, Melbye M. Brain. 2019 May 13. pii: awz088. doi: 10.1093/brain/awz088. [Epub ahead of print]

Multiple sclerosis is a disease with a highly variable incidence worldwide. While knowledge about multiple sclerosis risk factors has grown over the years, the aetiology of multiple sclerosis has still not been fully established. We examined multiple sclerosis incidence rates among first-generation immigrants in Denmark, a high-incidence country, and their Danish-born children (second-generation immigrants), to evaluate the importance and timing of exposure to environmental factors in the aetiology of multiple sclerosis. By means of the Danish Civil Registration System we identified 9 121 187 individuals living in Denmark between 1968 and 2015, including 1 176 419 first-generation and 184 282 second-generation immigrants. Study participants were followed for multiple sclerosis in the Danish Multiple Sclerosis Registry from 1968 to 2015. The relative risk (RR) of multiple sclerosis according to immigration status was estimated. Altogether, 16 905 cases of multiple sclerosis were identified in the study cohort, 578 among first-generation and 106 among second-generation immigrants. Multiple sclerosis risk among first-generation immigrants whose parents were born in low, intermediate and high multiple sclerosis risk areas were 21% (RR = 0.21; 95% CI: 0.16-0.28), 43% (RR = 0.43; 95% CI: 0.36-0.50) and 75% (RR = 0.75; 95% CI: 0.67-0.83), respectively, of that among ethnic Danes (test for trend P < 0.0001).

First-generation immigrants arriving in Denmark before age 15 years had a multiple sclerosis risk higher than that in their country of birth but lower than that in Denmark, reaching on average 69% of the multiple sclerosis risk among ethnic Danes (RR = 0.69; 95% CI: 0.55-0.87). 

Multiple sclerosis risk among individuals who came to Denmark at a later age remained closer to that of their country of birth, corresponding to 45% of the multiple sclerosis risk among ethnic Danes (RR = 0.45; 95% CI: 0.41-0.49).

Stratifying second-generation immigrants according to parental multiple sclerosis risk revealed an inverse association between multiple sclerosis risk and the multiple sclerosis risk at the parental birthplace (test for trend P = 0.007). Notably, multiple sclerosis risk among second-generation immigrants whose parents were born in low multiple sclerosis risk areas was doubled (RR = 2.01; 95% CI: 1.40–2.87),

The study supports the idea that environmental factors exerting their role in childhood or adolescence may be of aetiological relevance in multiple sclerosis.

So environment is important and says MS susceptibility is modifyable if we know the right environmental factors to deal with. then you can prevent MS. This study supports what DRK said a while ago when looking at the East London population in that seconda generation immigrants get more MS than the first generation. This current study goes further and shows that age of immigration is important, but we have known this from much earlier studies`

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14 comments

  • Totally agree. Neither I nor my family even knew what MS was when I was diagnosed and this includes extended family. So I’m certain it was the environment for me.

  • I love this blog but this title does a disservice to people with MS. Making a leap from geographical findings to “ms genetic risk is modifiable” is unfair. By the time a person knows about their genetic risk they can’t siddenly change where they lived as a child, can they? As someone with ms who is convinced it is largely genetic (mother and cousins had it) I am looking for truly modifiable factors I can practically implement to protect my child in the future. I can’t change where she’s loved so far. Me personally took vitamin d for years as it was the only practically environmental modifier I knew and still got the bloody disease. Telling someone they could have changed their ms risk factor by doing something differently a long time ago they had no control over and can’t undo isn’t really fair. It’s an interesting study but one of those that excites academics and is useless to those with a real genetic risk. A better title would have been something like “this gives us researchers clues on what to study and gets us closer to finding the cause”. Not one that suggests patients have any control at all. Sorry I absolutely love this blog always give good feedback but must give feedback here please take a little more care not to upset patients. This title was a “bait and switch”.

    • It does not say there is anything they could have done. It is saying there is something that can be done for future generations and it is not all written in the genes, it is modifiable.

      It again shows that the greatest influence on MS is geography, if we can identify what it is in the geography that matters, then the information can be used to avoid MS in future generations. It also shows the effect of geography only works when you are young/ before you are born. The egg you grew from was formed before your mother was born so effects may stretch over generations. There is nothing you can modify if it occurred before you were born.

  • This can surely only be interpretted with caution; I mean many people have clinically silent MS their whole life, or have only mild symptoms that never lead to a diagnosis? That must muddy the waters a lot.

    Until we know the environmental factors in question, we surely cannot begin to speak of risk being modifiable. Until then, we’re liable to do something analogous to when they blamed toads for warts!

    • All the data shows that the best way to reduce your risk of MS is to be born and live at the equator. This has been observed in the Australian MS incidence since it was first detected in the 1940’s. The effect is seen with latitude and cloud cover, and is most likely due to the length of the winter and light/UV exposure, thus the thinking that vitamin d is important.

  • I thought about genetic/environmental risk a lot. We didn’t want kids anyway, but I don’t think fear of passing on genes would have put me off. I thought that there are likely to be many others with even more risk genes for MS than I – given I’m the first in my family to have MS – and they’re completely unaware of it, they just had better luck with the rolls of the dice. Knowing the environmental factors could help prevent MS. It’s an important area. Especially if an effective antiviral against EBV might be all it takes to break the disease pathology before it gets off the ground…

    • “It’s an important area. Especially if an effective antiviral against EBV might be all it takes to break the disease pathology before it gets off the ground…”

      It could work as treatment also..just as EBV immuno cancer therapies.

      “The primary objective of Atara’s ongoing ATA188 Phase 1 dose-escalating clinical study is to evaluate safety and tolerability for patients with progressive MS. Initial safety results showed that the first two dose cohorts of ATA188 were well tolerated with no dose-limiting toxicities and no grade ≥3 treatment-emergent adverse events. The study is continuing with the objective of identifying a recommended Phase 2 dose. In addition, a randomized double-blind, placebo-controlled dose-expansion period for this study is now planned following the completion of the dose escalation phase.”

      http://investors.atarabio.com/news-releases/news-release-details/atara-biotherapeutics-announces-presentation-initial-ata188

  • Or equally a virus is the cause that isn’t prevalent in low risk countries. For instance ms didn’t exist in Australia until migration of English speaking people.

  • “This current study goes further and shows that age of immigration is important, but we have known this from much earlier studies`”

    Exactly more pointless research…filling up blank paper.

    Meanwhile a man in India posted to HSCT forum..never thought such damage was possible in 12 yrs. MS but
    I guess this is the illusion everyone plies to justify drug costs use and costs.

    “I want to ask that ,if there is a cure after 12 yrs with ms, and damages are… can’t speak, can’t see, can’t move hands,legs and head . Listening and understanding is well,and can answer raising her right hand fingers. Thanking you all.”

  • The problem of course is demonstrating which environmental factors influence susceptibility and disease progression, especially if we have to generate the evidence via randomised, double-blind, placebo controlled studies for the evidence to be taken seriously.

    The epidemiological data certainly suggests to me that lifestyle factors (e.g diet). and / or exposure to a viral or bacterial agent could be factors causing onset and progression.

  • Can environment cause cellular stress?

    Cellular Stress, Not Infection, May Rouse Slumbering MS-Linked Retroviruses

    One possibility, suggested by several recent studies, is that human endogenous retroviruses (HERVs) are activated by infectious phenomena. Another possibility is that HERVs become active when cellular stress causes inflammatory responses to become dysregulated. This second possibility has just been proposed by scientists based at the Institut Pasteur.
    https://www.genengnews.com/news/stress-not-infection-may-rouse-slumbering-ms-linked-retroviruses/?fbclid=IwAR0VMLRlpqbARYLjmduJvyB9-1y0WUa9GGmpv5qE8N1O6BgalGoWeX9NlIo

    • Yes, GeNeuro are developing Temelimab which targets the MSRV-Env protein. It is showing promise in MS. They have also just completed a phase II study in type 1 diabetes which provided some interesting results.

      It has been proposed that EBV-generated miRNAs could be involved with both adaptive immune activation and HERV de-repression and transcriptional activation.

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