rs35044562. However, the effect is probably very small compared to environmental factors (e.g. disrupted innate immunity due to insulin resistance or obesity).
The highest genetic contribution to any common disease seems HLA-B27 ~ ankylosing spondylitis, closely followed by HLA II ~ type 1 diabetes. But in these cases, still, it just explains around 15% of the variance. After these big contributors, there's a long list of genes that contribute with exponentially diminishing effect sizes. And the overall contribution of genetics never exceeds 50%. It's good to understand some disease factors, but interventions are much simpler from the environmental side of things.
I'm surprised that COVID is not linked to HLA in any meaningful way. Probably the study from Pääbo is not accounting for HLA because of lack of imputed haplotypes. It's a bit of a statistics smell that there's no association whatsoever. Nothing shows up in his chr6 region in the Manhattan plot. All infectious agents have some correlation. That's the whole point of HLA, implementing different strategies against them.
For example, HLA-B57 and B27 tend to be super-responders against HIV. This haplotype seems to be trading more autoimmunity risk in exchange for better protection against rapidly mutating viruses. It expanded quite quickly around Northern Europe around 10000 years ago, probably due to another pandemic.
We don't know, probably it doesn't. I was simply complaining about the lack of HLA correlations in the paper, which is suspicious. Probably they didn't type or impute HLA haplotypes.
My HLA-B27 example was actually a positive one. It gives you higher chances of a good outcome if infected by HIV.
Another paper, with a small sample size, claims HLA-B44 and C01 are susceptible [1].
I work with the Oxford vaccine group, and I am quite interested in this effect, including in vaccinated patients. It's pretty well known bad vaccine efficiency and side effects will correlate very strongly with HLA, and with thymic involution.
Sadly everything is quite chaotic at the minute and it's difficult to get samples and funding for these ideas. If we were more advanced, we would get be classifying vulnerable patients and asking them to shield according to HLA and immunoageing/dysfunction markers.
So as I understand you are involved by the vaccine that AstraZeneca is also behind. So I kind of understand (well, as much as layman can understand, lol) the vaccine that Pfizer and Moderna works. I guess it is a bit better explained on Wikipedia. So their vaccines inject mRNA to our cells which start producing antibodies. While this is brand new kind of vaccine, it's hard to know long term effects of it, but there's a chance that it could cause an autoimmune disease.
When reading about vaccine created by Oxford, the biggest concern seems to be that people could have or develop antibodies for the adenovirus after first dose. I'm guessing someone with HLA-B27 has even a higher chance of doing that. I understand that, but I'm still not understanding how it works. Is it same as the mRNA vaccine, with the difference that the adenovirus is just used to deliver it?
I have collaborators in the vaccine group, but I'm not directly involved in the trial. In fact, I think the Oxford vaccine has 2 potential design issues, 1 of which is shared with all other vaccines.
The first issue is what you pointed out. Adenovirus delivery is potentially more risky. I'm incidentally also HLA-B27, and I will personally stay away from it.
The second issue, shared with all other vaccines, is that IMHO they should not have vaccinated us for the whole spike protein, but just for some fragment. The spike protein contains some mimotopes to confuse the immune system, and I'm worried that this might also be a source of autoimmunity in very rare cases. Naturally, because vaccines had to be rushed, this was not easy to account for.
Nonetheless, they all seem safe. Theoretically, mRNA ones might be safer, unless there's gene transfer/integration of mRNA into cells. But this is a very exotic issue unlikely to cause problems.
Eg. Part of the redacting were removed and this was an example:
> But there are a few shreds of information that are really, genuinely new, and they’re damning of the president. Namely: Trump had direct knowledge of Roger Stone’s outreach to WikiLeaks, according to multiple witnesses interviewed by Mueller. He encouraged that outreach and asked his campaign chairman to pursue it further, those witnesses said. And Mueller’s office appears to have strongly suspected, without putting it in so many words, that Trump lied to the special counsel in his written answers to Mueller’s questions about the Stone affair.
I'm not going to read the version where they hide the important bits.
The governor of that swing state happened to be the brother of the Republican presidential candidate. That governor's secretary of state also purged the registrations of 90,000 black voters months before the election.
Al Gore never claimed that he was the only legitimate winner months before the election began and that any result in which he lost would be fraudulent.
This is both-sidesism, which is an intellectually lazy excuse to avoid taking action while appearing morally above the fray.
Trump literally uses cult-like techniques to control his followers, traffics in conspiracy theories, attacks as "fake" any news media which doesn't praise him effusively, and is actively undermining democracy itself by claiming that any votes against him are illegitimate. There is no vaguely liberal or left politician in US history who has done what Trump has.
Fascism is a political strategy involving fear of change and scapegoating. If you’re trying to imply that use of force automatically translates to fascism, then you need to consider situations of community defense against fascists, which ultimately requires force. Self-defense and defending democratic rights is quite different from terroristic violence in the service of subverting democratic and human rights.
I reserve the term “violence” to situations described in
Hannah Arendt‘s similarly-named essay, in which terroristic violence has historically been used by failing dictators against the legitimate power of the people as a whole.
If using violence to combat opposing political speech isn't your definition of fascism, then it's as equally sinister and takes us to an equally dark place.
We have seen many examples in the last few years of people feeling so entitled to combat what they consider fascism, that they use violence against anyone they perceive as the enemy.
Maybe we don't agree on the definition of words, but this is a bad development.
Ethics applies here just as well. You are trying to equivocate the actions of those who actually attempt to kill those who disagree politically (aka “terrorism”) with attempts at eliminating platforms for wide dissemination of speech.
