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Comment by Karrot_Kream | Hacker News Reader

> I'm just saying that IMHO it's not a definitive study

It's not, and I'm disappointed in the submission's title. The paper's title is "No evidence that vitamin D is able to prevent or affect the severity of COVID-19 in individuals with European ancestry: a Mendelian randomisation study of open data" Which is correct; no evidence was found in the study that correlated Vitamin D levels with Covid severity. But yes, this is not an RCT and we cannot use the study's conclusion to definitively disqualify Vitamin D supplementation.

> it was not even based on data about actual vitamin D levels

Medelian Randomization is a pretty well-established study technique which _isn't_ an RCT, but often yields results close to them. It's a bit simplistic to say that "the data isn't about actual Vitamin D levels", when MR is specifically a study method used to step around direct measurements to analyze effect.

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> "the data isn't about actual Vitamin D levels", when MR is specifically a study method used to step around direct measurements t

Yeah, this would make sense if you ignored all dietary and solar variations in Vitamin D productions. So yeah, this person has a bias towards high or low levels but you're not actually measuring it

I don't think it's an honest assessment

This would only make a difference if P(low dietary vitd) or P(low solar intake) is small (and assuming dietary values/solar values are independent of having a genetic disposition to lower vitd levels and independent of COVID prevalence), which I don't think is true. What I think may be true and may not be compensated for by the study is the fact that individuals with genetic disposition for lower vitd levels may be supplementing (through either greater sunlight exposure or dietary supplements) to bring up their vitd levels, even before COVID came onto the world stage.

> I don't think it's an honest assessment

Of what though? This is just a study trying to prove a correlation with VitD deficiency and COVID prevalence, of which they couldn't find any. Any stronger conclusion is out of the scope of the paper.

> Yeah, this would make sense if you ignored all dietary and solar variations in Vitamin D productions

No, actually, MR specifically accounts for these variations.

However, one idea (one that would need a lot of evidence in my opinion, but to give you a clearer picture) that is not captured by MR is horizontal pleiotropy. So, if the genetic variants used in this study e.g. actually cause someone to seek out dietary modifications/solar augmentation of vitamin D, that would not be accounted for here.

I don't think the biology in this case allows for that to any significant degree, but I'm not an expert in vitamin D metabolism/action or COVID.

> I don't think it's an honest assessment

The title here is maybe a bit simplified, but the paper is quite honest about its weaknesses if you read it in its entirety.

> MR specifically accounts for these variations.

How exactly? The only mention I see is using the British Biobank data which is 10-15 years old

Well, it's a fundamental technique in statistical genetics, so the paper doesn't explain it in depth. MR uses the technique of instrumental variables. [1] looks like a good explanation.

The basic idea is to identify a variable Z (genotype, in the case of MR) that causally impacts your outcome Y (COVID, in this case) only through your exposure X (vitamin D levels). If you can find and measure such a variable Z (which meets a few other conditions [2]), then you can robustly identify whether X has a causal impact on Y only from observational data.

[1] https://www.youtube.com/watch?v=NLgB2WGGKUw

[2] https://en.wikipedia.org/wiki/Instrumental_variables_estimat...

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