Comment by AnthonBerg | Hacker News Reader

Comment by AnthonBerg | Hacker News Reader

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

DOI: 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!!

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.

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.

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/

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

I found that way of writing terribly arrogant and annoying, like a smart 15-year-old.

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?

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.

...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.

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.

That seems like a problem with society (maybe an academia) more than 15 year olds no?

Besides, a lot of people interested in a wild theory greatly ups the chances someone gets funding to test the hypothesis, no?

Thank you for your honest perspective! Sincere thanks. I guess it’s the approach of 45 years of age that I am unfazed.

I’ve heard a number of times that my persona in writing absolutely does not make sense to some people – until they meet me.

I think I can assure you of my non-arrogance. The wry, cynical, even flippant? note is directed at myself. My limitations and recklessness and jumping to conclusions.

If you find me, I offer you a cup of coffee. In return I’d like an equally honest reassessment.

(Full sincerity here!)

edit; Ah. Also. Another thing I can assure you of: Sometimes, afterwards, I come across my own writing and find it awful. in exactly that way. Like an annoying and arrogant 15yo had written it. Which is my greatest fear. To become that 15yo again, the person I certainly was for a decade or so. (Starting at around age 12-ish.) I knew I was annoying but I didn’t know I was arrogant. It turns out the two were related.

IMO there has been a growing undercurrent, in online discussions forums, of disdain for writing and authors who aren’t well-established as authority figures or known experts in their field. Tone and word choice is narrowing into a conversational style, and anyone “straying from the pack” sticks out like a sore thumb in online boards.

Anything sarcastic or playful can be perceived as insincere.

I’d be happy to read more of your thoughts—you should keep writing.

You should just leave it at "people like different things" instead of making claims about why people don't like something (especially something that you like).

Because now you invite more negativity (on top of the original negativity and now yours) as people who didn't like their writing may now want to defend themself because they just didn't like the style and aren't part of some "growing undercurrent" who can't appreciate his brilliance because he's not "well-established nor a known expert".

Maybe they just think the writing is overwrought like when you outgrow John Scalzi's lamewad writing after briefly finding it clever in Old Man's War? (I think that's a decent place to end this because Scalzi is a very successful author.)

I find your writing - at least in these 2 comments - amusing and insightful to read. thank you

You write like why the lucky stiff the author of why's poignant guide.

Takes all kinds. I'm +1 the blog.

I find your harshness, in response to a purely positive and informative comment, to be terribly arrogant and annoying, like someone pretending to be as smart as a smart 15 year old.

I always think when people react so negatively on text (comments, articles, blog-posts), they reveal a lot about themselves.

Not in the sense of a "moral high-ground" type of argument that is usually aimed for with this phrasing.

Rather: To be so convinced about knowing how a text must have been meant or what the author must have thought that one writes a very absolute judgmental statement, the reactor is most likely either very narrow-minded and isn't capable of dealing with thoughts that are not the first to salute ones mind, or, they reveal that in their mind their proposed "intention" or background is the truth, because they themselves would have only written a similar text with that intention or background... so either way: people being so negative (especially to strangers on the internet) about positive things, for no reason & without being asked, are just full of... themselves... (like me, i mean who am i to ramble this irrelevant stuff).

(I was about to delete it again, as i usually do after writing things down & then realizing they're stupid or not polished enough to convey the idea, but hey, i am also just a 15-year old arrogant mind that already wasted his time... so now, that you are here, i successfully also wasted yours. Your welcome!)

I am very glad for your understanding. No, no blog at this time. Noted; humbly.

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