Astounding article on bbc saying that intense exercise can give rise to increased risk of mnd in those who are genetically vulnerable. Apparently 1 in 300 get the disease and athletes higher risk. Astonishing.
Many may know this awful disease and any research that reduces it's risk has to be welcomed . Had a colleague aged 50 who self diagnosed this and flew off to switzerland.
OK I've had a read through the original article:
https://www.sciencedirect.com/science/article/pii/S2352396421001900#bib0044
Overall their genetic correlations look pretty weak to me (but note that genome-wide association studies are
not my specialty). Most notably, their purported correlation between genetic variants that are linked to strenuous exercise and variants that are linked to ALS (Fig 2a) are dominated by the effect of a single variant (SNP = single nucleotide polymorphism = change at a single "letter" in the DNA). Remove that SNP from consideration and I'm skeptical that there would be a significant correlation, especially since their significance is already pretty weak. Now, that does, on the other hand, imply that perhaps at least this one SNP needs to be considered as possibly linking strenuous exercise to ALS. However, I would guess that that SNP is rare enough not to be a concern for most people. That is, carry on exercising unless you have a reason to suspect you might be genetically susceptible.
Their methods are frustratingly vague for the part that I
could provide better comment on (were I asked to review the paper I would have taken them to task on that), which is looking at whether genes whose expression changes after exercise are also linked to ALS. They look at "pathways", which are groups of proteins that work together to accomplish some task. After reading this paper as well as a previous one that they refer to, I'm still not clear on how exactly they choose the pathways, but it's based on the genes that they observe significantly different levels of expression following exercise. Anyway, they then check whether these pathways have more ALS-related genes encoding the proteins than expected, and indeed a few interesting ones pop out. They also separately ask whether genes that are related to ALS tend to be expressed differently following exercise, and yes they find that more than half of them are and by sort of "shuffling the deck" of their data, the confirm that this is more than you would expect by chance. My problems here are two-fold. 1) These are indeed interesting results but I see no reason to link change in expression of ALS-related genes to the development of the disease, i.e. this is very much correlation and not causation. 2) Their gene expression data is
weird (Fig 3c)...it's bizarre to see so many genes with exactly the same change in expression and nobody rounds this kind of data to the nearest nice number. I am
extremely suspicious of that data. It looks like an accidental MS Excel mistake or a rookie programming error. It's unfortunate that they don't provide more detail to maybe justify it.
Anyway, as mentioned, my takeaway is, unless you have reason to suspect that you're susceptible, I wouldn't take this as reason to stop exercising. If in doubt, contact your doctor.