I'm contemplating GLP-1 treatment but I'm concerned that it will accidentally decrease the obsession that I have that makes me good at my job.
N=1, I've been on GLP-1s for a long time and continue to be an obsessive.
Readit Newsgraboy commented on Can Ozempic Cure Addiction? newyorker.com/magazine/20... · Posted by u/adrianhon
graboy commented on Cardiovascular disease is a solved problem totalhealthoptimization.c... · Posted by u/brandonb
It seems you are confusing mendelian randomization for specific alleles associated with LDL-C production and conflating that with mendelian randomization somehow controlling genetic confounding of heart disease. The control is for the LDL production, not heart disease.
Here is a simple primer on mendelian randomization: https://www.psomagen.com/blog/what-is-mendelian-randomizatio...
Please review the key principles and assumptions section. Using MR to control for genetic confounding of heart disease fails all assumptions. Thats why it quite directly does not follow.
This is why the paper presented does not support the claim that LDL is the sole source of heart disease. I'd be interested to hear what the authors of that paper (which is legitimate) think about it being used to support the OP's claim because "mendelian randomization".
> This is why the paper presented does not support the claim that LDL is the sole source of heart disease
Is that what we were arguing about? I guess it was. At some point in thinking about this my frame must have shifted into agreement with you. Of course there are other causes of heart disease besides LDL, like blood pressure, duh. The smooth dose response is about the particular gene not being linked to heart disease through something other than LDL, roughly.
graboy commented on Cardiovascular disease is a solved problem totalhealthoptimization.c... · Posted by u/brandonb
Graboy has provided the citation I would have given, as well as an excellent explanation. I’m not sure what you mean by “heart disease is clearly not Mendelian”.
What do you think of Dr. Schooling's response that the Mendellian effects might be inflated? I think they had a good defense but was not entirely convinced they hadn't sidestepped the issue that Schooling was getting at, wasn't sure either way.
graboy commented on Cardiovascular disease is a solved problem totalhealthoptimization.c... · Posted by u/brandonb
Mendelian is characterized by effects having strong influence from a single gene. Heart disease is clearly more complex than gene -> heart disease. I thought that was basic enough that I didn't need to explain it. But here goes...
A clinical score changing with treatment is not unconfounded by mendelian randomization. When the genetics are clearly more complex than what you are mathematically randomizing for, the control doesn't solve the confounding. eg you haven't suddenly "proven" the effects are non-genetic. We already knew heart disease is non-mendelian. But showing something is non-mendelian doesn't mean you've shown it's not genetic. I hope that clarifies, because I'm not sure I can explain it to you in simpler terms.
I think maybe you are saying that there may be some way that the genes affect heart disease not through LDL, and therefore MR does not apply because the "exclusion restriction" [1] fails here? Or are you talking about a different assumption?
The cited study addresses this, which is why I pointed to figure 3. They argue that if genes were causing heart disease not through LDL in any meaningful way, you wouldn't expect such a clean dose-response consistency across different genetic variants - it would be more jagged.
[1] https://en.wikipedia.org/wiki/Mendelian_randomization#Defini...
graboy commented on Cardiovascular disease is a solved problem totalhealthoptimization.c... · Posted by u/brandonb
Heart disease is clearly not Mendelian. So, unless you have a specific well-designed study to cite, that is a non-argument.
https://www.jacc.org/doi/10.1016/j.jacc.2012.09.017
Across different genetic variants, lower lifetime LDL -> lower risk of death. Check out figure 3.
The causality of LDL -> plaque buildup -> 55-60% [1] of heart disease related deaths is also well understood, so it seems clear to me that preventing plaque buildup in the first place prevents over half of heart disease related deaths.
Would like to know if you disagree, "Minimize LDL at all costs" goes current mainstream medical guidance, so I'd like to disconfirm my beliefs if possible.
[1] Number from deep research.
graboy commented on Cardiovascular disease is a solved problem totalhealthoptimization.c... · Posted by u/brandonb
Here’s a counterpoint if anyone is interested:
https://www.midwesterndoctor.com/p/why-are-statins-so-danger...
I’m not saying either side is right but when it comes to your health why not evaluate as many opinions as possible.
Here is the chief editor of JAMA internal medicine arguing there is not enough evidence to prescribe statins for primary prevention in those 40+: https://www.natap.org/2016/HIV/ied160021.pdf
graboy commented on Russia Creates New Military Branch Dedicated to Drone Warfare twz.com/news-features/rus... · Posted by u/breve
Yeah I am mean when your political opinions get niche you start asking yourself: what am I? A factory? A cult? A sect? One guy? What's the difference here? It's all about your replicators.
Where it reaaaaally gets weird with drones are of course, it's better if the other guy doesn't find you. What if they NEVER find you?
what?
Gelesis100, another oral hydrogel, I understand is not very effective, I wonder what makes this one different?
To the extent empathy is "do onto others as others would do onto you", empathy has a moral justification derived from Kant's categorical imperative.
Deleted Comment