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Viral DNA in the human genome linked to major psychiatric disorders
- AnthonBerg 2y agoFor 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 agoVery 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 agoThank 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 agoDo you blog? I'd love to read more, and I really enjoy your writing style.
- kylebenzle 2y agoI found that way of writing terribly arrogant and annoying, like a smart 15-year-old.
- suoduandao3 2y agoI 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 agoThe 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 agobecase 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 agoThe 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/
- im3w1l 2y agoSo uhm, can/should we start cutting these proviruses(?) out of our genomes? Unintended consequences?
- Feuilles_Mortes 2y agoDefinitely not. Current estimates put viral DNA at about 8% of the human genome.
- im3w1l 2y agoWould it be possible to consider them separately though? Like maybe it will turn out that say 10% of them are beneficial, 65% of them are neutral (either they do nothing at all or a mixture of benefit and harm), and 25% are slightly bad for us (can't be too harmful or we would have already known ig).
- biophysboy 2y agoDelivering gene therapies into brain cells is a non-trivial task. Also, there's alternatives to cutting the original sequence out; you can also dampen the transcribed RNA with downstream therapies.
- suoduandao3 2y agoI thought this was more of a 'designer babies' suggestion than a 'mess with the source code after it's finished compiling' one.
- AdamN 2y ago'Bad' is notoriously hard to figure out. It might be good for the group to have a few people with major psychiatric disorders even if it's not ideal for that individual or the people who have to directly interact with them.
- COGlory 2y agoWe can't (currently) cut them out because there's too many cells and they're brain cells. But if we could make complementary RNA, that could potentially neutralize them.
- ldehaan 2y ago[dead]
- maratc 2y agoThis kind of science leaves me with lots and lots of questions. E.g.: As our understanding of DNA progresses, and we link more and more of it to different traits, will we eventually get into a situation where a swab on the water glass tells potential employer much more than the interview? Or: imagine that in addition to the discovery "viral DNA in the human genome linked to major psychiatric disorders" there's a discovery that "this viral DNA is much more prevalent in [a certain population]". What will be the consequences of this?
- viraptor 2y ago> where a swab on the water glass tells potential employer much more than the interview? More likely RNA, because DNA doesn't mean traits are actually active. Also, only if you believe nature>>nurture and that experience doesn't matter. The level of understanding of your issues and how to counteract them makes a difference too. In practice you probably want someone with issues they know how to cope with and lots of enthusiasm for $job rather than a rando with great generic potential and hating every minute at work.
- maratc 2y ago> only if you believe nature>>nurture Imagine a situation where there are two presidential candidates, who are both somewhat bad, and then it becomes a matter of public knowledge that one of them has "Viral DNA in [his] genome linked to major psychiatric disorders". I don't think what I do or don't believe would matter in the larger scheme of things.
- ndynan 2y agoMaybe someone can provide a better understanding, I'm a clinical psych doctoral student, but this is outside my area of research + methods. On very quick review, it looks like there are is significant association between HERV genetic factors and specific diagnoses given PIP. However, what's not clear to me is effect size or correlation coefficient. I'm not sure if I'm missing this or it's not reports. There might be a relationship, but at a very small percentage.
- Slava_Propanei 2y ago[dead]
- andrewflnr 2y agoI'm sure this is good research but I'm also sure it's the basis of the next generation of antivax propaganda.
- gradientsrneat 2y agoAs another commenter pointed out, the expression of these genes doesn't cause inflammation. So, maybe the antivaxxers will ignore it, as it doesn't fit well enough into their existing framework.
- andrewflnr 2y agoIf antivaxxers held themselves to a consistent model, they would be gone by now. For instance, long ago it used to be about the mercury based preservative that's basically never used now, but somehow vaccines are still evil somehow. Some other way, for sure. They've just got "vaccine = bad" stuck in their head and they'll grab any scrap of info that confirms their bias.
- byteknight 2y agoSomeone with a better grasp of the scientific method perhaps you can answer this. I am under the impression we (science) hasn't definitively determined causation for depression. How can you definitively determine a link without knowing the underlying causes. It would imply you know how it works, doesn't it?
- suoduandao3 2y agoMy understanding is they've demonstrated a correlation. I don't think they've made any claims about causation.
- xkcd-sucks 2y ago> Someone with a better grasp of the scientific method perhaps you can answer this. As a (recovered, former) neurobio phd it seems the "grasp" is mostly there + the clarity you want just doesn't exist here I.e., the concept of "depression" is pretty hard to nail down quantitatively in the first place: The best model we've got is a kind of self-contained proven-by-internal-self-consistency thing bootstrapped from questionnaires, which is of course further abstracted away onto those model systems we're allowed to kill: For example, calling "how long do mice swim before giving up if you chuck them into a tank of water" is roughly equated to "amount of depression" (this is oversimplified a bit; you correlate a bunch of those measures etc. but still a lot of very weak signals). Even "relevant quantitative data" like fMRI / ECoG is bootstrapped from questionnaires when it's something undefinable like "depression" Which isn't the end of the world, everything started out like this, it just sucks when people take these results too seriously or infer too much from them. And even the human black-box stuff in the DSM manuals admits a lot of different subtypes, lots of different and sometimes opposite symptom clusters, etc. It is entirely possible that mechanistically "depression" is a diverse group of mechanisms all boxed up into the most familiar mainstream concept/word.
- byteknight 2y agoFirstly, thank you. > For example, calling "how long do mice swim before giving up if you chuck them into a tank of water" is roughly equated to "amount of depression" (this is oversimplified a bit; you correlate a bunch of those measures etc. but still a lot of very weak signals). Do I understand this? A purely reductionist view of my understanding: this is quantified as "the amount of will to live"? If my understanding is proper, how do you measure this without killing people? I grok that it is an extreme example, I am attempting to glean applicability of such an experiment to humans. > And even the human black-box stuff in the DSM manuals admits a lot of different subtypes, lots of different and sometimes opposite symptom clusters, etc. It is entirely possible that mechanistically "depression" is a diverse group of mechanisms all boxed up into the most familiar mainstream concept/word. Totally unrelated, but wife is an LCSW and I've glanced at the DSM. I've become convinced that book is near entirely for insurance purposes, similar to the ICD-10. ICD-10: W220.2XD: Walked into lamppost, subsequent encounter.
- deleted 2y ago[deleted]
- freshpretzels 2y agoCould CRISPR or a tool like it be used to “cut out” these parts of someone’s DNA and cure them from those disorders?
- londons_explore 2y agoHow sure are we that this viral DNA in our genome isn't occasionally activated to make fully fledged viruses?
- londons_explore 2y agoThis embedded viral DNA would presumably make all cells more susceptible to similar real viruses, since the MHC class I signalling methods couldn't be used to find them.
- marmadukester39 2y agoJust for fun - does this sound like what the remnants of ancient genetic engineering experiments on primates to increase their intelligence might look like to anyone else?
- gradientsrneat 2y agoI'm partial to the null hypothesis, but one thing to check would be junk DNA in other extant species, and ancient human remains.
- r0ze-at-hn 2y agoActual paper: https://www.nature.com/articles/s41467-024-48153-z https://www.nature.com/articles/s41467-024-48153-z
- AndrewKemendo 2y agoThis one is still in my “to read” queue from last week For anyone that’s read it, I’m curious did they compare relative percentages of these DNA between haplogroups Eg. Percentage of antisocial DNA in Europe vs Asia vs Bantu etc…
- de_layer 2y agoAmateur question: if we've retained these ostensibly dangerous or at least deleterious viral codes in our DNA, is there any reason why these virii don't serve a important evolutionary or remedial (maybe crisis) purpose?
- kuu 2y agoMaybe it's the other way around: there wasn't enough environmental pressure to eliminate this trait.
- gradus_ad 2y agoMen who were prone to alternative/extreme states of consciousness would have been better able to summon up the wild emotions necessary for savagery and violence, making them better fighters and hence giving them better mating prospects.
- ossobuco 2y agosomehow I doubt that someone with depression/bipolar disorder would be the best candidate to be a warrior
- loa_in_ 2y agoThey would be constantly vigilant and unpredictable to someone unfamiliar with that particular trait. When wandering you might only have yourself as a reference so they would be a counter to that
- nullindividual 2y ago> They would be constantly vigilant If they've even lived long enough, no absolutely not. Unless you think someone who is routinely depressed is 'vigilant'. [Hypo]mania is not the primary state of a bipolar patient. Can't speak to schizophrenia, but for those I've seen with that illness, functioning isn't their primary state, either.
- zdragnar 2y ago
- richardlblair 2y agoOhhhh, so it's this DNA thing and not the fact that my Daddy didn't love me?
- dailykoder 2y agoCrazy hypothesis: What if it ain't that simple?
- richardlblair 2y agoIn what sense? The DNA or my Daddy? Because legit, my father was an acholohic and generally absent. It really fucked me up.
- labrador 2y agoI'm sorry that happened to you. I can't speak for all bipolar alcoholics, but I sought treatment and now I've made amends with my son and we have a good relationship if that helps at all.
- richardlblair 2y agoThat's really great. Not enough people pull themselves up, make amends, and do better. You're one of the good ones <3
- labrador 2y agoI'm trying. Thanks and good luck.
- dailykoder 2y agoBoth. Sure we make huge progress in depression research and brain research in general, but there are so many environmental things happening, like yours for example, so just saying "oh yeah depression comes from that DNA" or "yeah that's just from your trauma. A lil therapy will heal everything" is just a bit short sigthed. So yeah, just saying that it's all very complex and we shouldn't really try to reduce this beast of a disease down to anything, because everyone has a different story. In the end I was just a little sarcastic, sorry
- vitorbaptistaa 2y agoIs it possible to check for the presence/absence of these using data from 23andme?
- mfld 2y agoThe SNPs can be found in the supplement, so you could check this. But why? Probably it would make more sense to check all risk alleles known to be associated with e.g. bipolar disorder to test for your own risk.
- MrGuts 2y agoDon't mind me, I'm just feeling a little Cro-Mag today.
- binary132 2y agoA literal wetware virus, so to speak
- AdmiralAsshat 2y agoHomo sapien mother glaring at Cro-magnon husband: "He doesn't get it from my side of the family!"
- usrnm 2y agoCromagnons are Homo sapiens, though
- addingadimensio 2y ago[dead]
- zxxh 2y agoWhere are the religious people admitting they were wrong? I was told god’s will existed, but here we see it doesn’t? Care to explain/apolgize? This is free speech.
- dudeinjapan 2y agoThe thought of ancient viruses in my DNA makes me even more depressed.
- ldehaan 2y ago[dead]