2011 proposal: environment is MS' main cause; genetics minor

[jimmylegs]

The major cause of multiple sclerosis is environmental: genetics has a minor role - Yes (2011)
http://journals.sagepub.com/doi/full/10 ... 8511421105

Proposal
It is clear that multiple sclerosis (MS) has a complex aetiology that involves both genetic and environmental factors and that both make a significant contribution to causation. However, the weight of evidence would favour a significantly greater role for the environment over genetics. There is now ample evidence for a profound effect of the environment on MS causality, with at least four and probably more factors directly contributing, with the reported effect sizes significantly greater than any identified genetic factor.

• latitude, sunlight exposure (UVR), and vitamin D (odds ratio [OR] ≈ 20);1
  
  prior Epstein–Barr Virus (EBV) infection timing and adaptive immune response to EBV (OR = 12.5);2
  
  cigarette smoking (OR = 1.4);2
  
  the hygiene hypothesis (OR ≈ 3).3

...
Conclusions
The weight of evidence would support the assertion that the environment is more important than genetics in the causation of MS. Environmental factors may provide >75% of the risk of developing MS. Although genetic factors are important and may play a significant role in the development of MS in individuals not exposed to the discussed environmental factors, they are by no means the major driver of MS causation in the vast majority of MS cases.

a few possibilities missing from this proposal, to my way of thinking anyway

[ElliotB]

Another great theory that makes as much sense as all the other theories that also make sense.


...that the environment is more important than genetics..

Perhaps scientists should carefully study the environments where there are zero cases of MS to get a better idea of what exactly is going on with their environments that protects these multiple population groups from getting MS and probably other illnesses. Surprised no one has done this yet. What are they waiting for?

[frodo]

If we consider Epstein-Barr virus as part of the environment, I think this statement is quite right.

[ElliotB]

Odd that they don't include diet/nutrition in the mix. To me, that would be a major factor unless they consider nutrition part of 'environment'.


An interesting comment, "the risk for siblings is 20–40 times the background population MS risk". To me this is very significant and contrary to commonly accepted thoughts on family risk.

An odd comment "It is important to note that there does not appear to be a genetically MS immune population" as this is absolutely not true. There are several population groups that have zero incidence of MS.

[Petr75]

Good article.

[Petr75]

2020 Apr
Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece
Environmental factors and risk of multiple sclerosis: Findings from meta-analyses and Mendelian randomization studies.
https://www.ncbi.nlm.nih.gov/pubmed/32249718

Abstract

Multiple sclerosis (MS) is a chronic demyelinating disease that is associated with permanent disability and low quality of life. Development of MS is attributed to a combination of genetic and environmental factors. Genome-wide association studies revealed more than 200 variants that are associated with risk of MS. An umbrella review showed that smoking, history of infectious mononucleosis, and anti-Epstein-Barr virus nuclear antigen (anti-EBNA) immunoglobulin G (IgG) seropositivity are credible risk factors of MS. In the present narrative review, we updated our published umbrella review, showing that body mass index in childhood and adolescence and anti-viral capsid antigen (anti-VCA) IgG seropositivity are additional credible risk factors of MS. In addition, we discuss the findings from Mendelian randomization studies, which present evidence for a potential causal role of serum vitamin D and adulthood body mass index on risk of MS. Finally, we discuss the potential limitations of meta-analyses, umbrella reviews, and Mendelian randomization studies in the search for risk factors of MS.