3 ms·

For convenience here’s the paper: Integrating human endogenous retroviruses into transcriptome-wide association studies highlights novel risk factors for major

For convenience here’s the paper: Integrating human endogenous retroviruses into transcriptome-wide association studies highlights novel risk factors for major psychiatric conditions by Duarte, Pain, Bendall & others: https://www.nature.com/articles/s41467-024-48153-z https://www.nature.com/articles/s41467-024-48153-z DOI: https://doi.org/10.1038/s41467-024-48153-z https://doi.org/10.1038/s41467-024-48153-z Open-access PDF. (Kudos to the medicalxpress writer for actually linking to the paper.) It seems to be quite readable. Just go fast enough to hydroplane on the surface, and jump as usual between the abstract, conclusion, abstract again, the middle part, the introduction and then put it away and sleep on it and come back to it and hydroplane and jump and… you know, all of that. Paper reading. Before reading, in the headline I sort of saw the question whether embedded viral DNA might be getting “deployed into prod” and causing bad stuff to happen. The second ha-ha-contrarian-I-am-very-intelligent thought—also cheap to produce—was whether the ability to survive a viral onslaught brutal enough for the virus to embed itself in its quarry might be an indication that ancestral individuals had a more robust and aggressive immune system than peers who didn’t survive to reproduce. And if this could show up as a runaway inflammatory response in the current era. (From what I understand, psychiatric disorders are very very often accompanied by neuroinflammation. Practically… always?) Such a great paper! I can speculate all this before I’ve even read the thing!!

Sakos 2y ago
Very interesting. The paper suggests though that for many of these it's unlikely it's due to an immune response: > It is not clear yet how the expression of the high confidence risk HERVs may play a role in psychiatric disorders. It was previously hypothesised that differential HERV expression in psychiatric cases was likely to be a by-product of immune responses against current or past infections34. Indeed, HERV expression is modulated by exposure to several pathogens35,36 and can activate inflammatory cascades37. This is an interesting theory that corroborates the fact that individuals with psychiatric disorders typically have higher incidences of infections38,39,40. However, our main analysis found that 1238 HERVs expressed in the brain are regulated in cis, some of which in association with risk for complex psychiatric traits. This indicates that there are HERV expression mechanisms directly contributing to disorder aetiology, that are not simply part of compensatory responses, or triggered by environmental factors.
- AnthonBerg 2y ago
  Thank you! To me, this is a great example of how to read papers. I think I skimmed that section a couple of times after writing the comment and it didn’t register. Thank you for making the connection.
fellerts 2y ago
Do you blog? I'd love to read more, and I really enjoy your writing style.
- kylebenzle 2y ago
  I found that way of writing terribly arrogant and annoying, like a smart 15-year-old.
  - suoduandao3 2y ago
    I rather enjoy talking to smart 15 year olds. They're curious about the world and more likely to have fresh takes. What's not to like?
    - dekhn 2y ago
      The problem is, even smart 15 year olds with fresh takes have to learn that no matter how interesting their ideas are, the scientific establishment is much more focused on finding good evidence to support incremental discoveries, rather than wide-eyed speculation about how complex biological processes work. (I was that 15 year old, and then after many years of sciencing, realized that it was nothing like what I thought, and that all my best ideas were either wrong, ahead of their time, or stolen by more accomplished scientists.
      - endofreach 2y ago
        ...and why not encourage to keep being like the 15 year old instead of accepting the status quo? The only problem i see here is, apparently this "establishment" got to you faster than you could remind yourself of what's truly important to you. I hate when people get discouraged by other people who mostly don't care that much & are afraid... they feed on your Neugier. Don't feed them. Feed other minds alike & screw the establishment.
        dekhn 2y ago
        becase when the 15 year old grows up, unless they are an absolute true genius (and even then), if they try to go around chasing wild ideas, they won't get funding or the ability to run the experiments to build a case for their hypothesis.
greg_V 2y ago
The inflammation vs. psychiatric disorders link is very interesting. See also some findings about the gut biome, which is also involved in the process: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830868/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830868/

Sakos 2y ago

Very interesting. The paper suggests though that for many of these it's unlikely it's due to an immune response: > It is not clear yet how the expression of the high confidence risk HERVs may play a role in psychiatric disorders. It was previously hypothesised that differential HERV expression in psychiatric cases was likely to be a by-product of immune responses against current or past infections34. Indeed, HERV expression is modulated by exposure to several pathogens35,36 and can activate inflammatory cascades37. This is an interesting theory that corroborates the fact that individuals with psychiatric disorders typically have higher incidences of infections38,39,40. However, our main analysis found that 1238 HERVs expressed in the brain are regulated in cis, some of which in association with risk for complex psychiatric traits. This indicates that there are HERV expression mechanisms directly contributing to disorder aetiology, that are not simply part of compensatory responses, or triggered by environmental factors.

AnthonBerg 2y ago
Thank you! To me, this is a great example of how to read papers. I think I skimmed that section a couple of times after writing the comment and it didn’t register. Thank you for making the connection.

fellerts 2y ago

Do you blog? I'd love to read more, and I really enjoy your writing style.

kylebenzle 2y ago
I found that way of writing terribly arrogant and annoying, like a smart 15-year-old.
- suoduandao3 2y ago
  I rather enjoy talking to smart 15 year olds. They're curious about the world and more likely to have fresh takes. What's not to like?
  - dekhn 2y ago
    The problem is, even smart 15 year olds with fresh takes have to learn that no matter how interesting their ideas are, the scientific establishment is much more focused on finding good evidence to support incremental discoveries, rather than wide-eyed speculation about how complex biological processes work. (I was that 15 year old, and then after many years of sciencing, realized that it was nothing like what I thought, and that all my best ideas were either wrong, ahead of their time, or stolen by more accomplished scientists.
    - endofreach 2y ago
      ...and why not encourage to keep being like the 15 year old instead of accepting the status quo? The only problem i see here is, apparently this "establishment" got to you faster than you could remind yourself of what's truly important to you. I hate when people get discouraged by other people who mostly don't care that much & are afraid... they feed on your Neugier. Don't feed them. Feed other minds alike & screw the establishment.
      - dekhn 2y ago
        becase when the 15 year old grows up, unless they are an absolute true genius (and even then), if they try to go around chasing wild ideas, they won't get funding or the ability to run the experiments to build a case for their hypothesis.

greg_V 2y ago

The inflammation vs. psychiatric disorders link is very interesting. See also some findings about the gut biome, which is also involved in the process: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830868/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830868/