r/science • u/sometimeshiny • 1d ago
Genetics Third-generation descendants of Holocaust survivors show DNA methylation differences in HPA-axis (NR3C1, FKBP5) and oxytocin-pathway genes, with greater openness to closeness but no increase in mental health symptoms.
https://www.nature.com/articles/s41598-025-12085-5223
u/throwawayfromPA1701 1d ago
I have been a skeptic of trauma being expressed in our genetics but the more I continue to read about this, the less skeptical I am.
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u/jittery_raccoon 21h ago
Trauma is stressful, both experiencing and reliving. The physical stress from trauma causes chemical production for many different processes. When the body produces chemicals inappropriate for the situation and then can't use, it accumulates and wrecks havoc on the body. The more stressed your body is, the harder it is for normal functions to function normally. One of the main functions of our body is to replicate DNA to keep living. Why wouldn't trauma effect your genes? Gene expression and passing on genes isn't magic. Your body is producing physical things. It's like overworking a machine. Eventually it won't work as well. And all of this physically gets passed onto your children. Think of it like a faulty copy machine. Would you rather make copies with a new one or the faulty one?
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u/ProofJournalist 15h ago
In general, stress is not producing anything inappropriate for the situation that calls forth stress. Stress has useful adaptive function, or we wouldn't have the response at all. The issue is when inappropriate stimuli trigger the respons3, not the response itself.
But yes, animals who live with constant stress exposure will adapt and pass on that genetic information. If you live in a drought, you better make drought ready babies.
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u/Big-Fill-4250 22h ago
Whats the control group? Did they test out to see if it had anything to do with survivor bias? I mean technically speaking those who survived were probably better at socializing no?
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u/Feisty-Resource-1274 22h ago
While that might play a role, researchers have seen similar epigentic changes in children born in NYC immediately following 9/11 which I feel like counts as a very randomized population sample
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u/SaltZookeepergame691 12h ago
They never adequately describe the control group. This is the sum information they provide:
185 were non-descendants (46.4% women, mean age = 29.34, SD = 3.10)
Unfortunately, that basically sums up the quality of science in this paper.
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u/CapoExplains 8h ago
What's inadequate about this description? They picked 185 people who were not descended from Holocaust survivors, 46.4% women, 53.6% men. Mean age of the control group was 29.34 with a standard deviation of 3.1.
When you call the description inadequate do you actually mean you feel they should have controlled for additional factors? That the description is perfectly adequate of the factors they were controlling for?
If so then fair enough but that's a concern with methodology, not with descriptiveness, and concerns with methodology really need to state what is missing and why that matters to be worthy of serious consideration.
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u/SaltZookeepergame691 7h ago edited 2h ago
What's inadequate about this description?
It is grossly, grossly insufficient to describe their suitability as controls. The only information we have about the controls is their mean age and SD, and that the authors state they are not descended from Holocaust survivors (without defining that - what actually defines a Holocaust survivor?)
There is no information on any other characteristic for either group:
- no demographic information (eg occupation, education, income/SES, race/ethnicity)
- no clinical or biological information (eg BMI, smoking status, alcohol status, chronic diseases, other trauma sources, medications, mental health diagnoses/treatments)
- no information on the single covariate they use (adverse childhood experiences)
- no information on any confounding genetic factors
This is all critical to a study that claims epigenetic inheritance that is trying to argue that observed changes are solely due to (ill-defined) trauma >= 2 generations previously. Either they didn't bother to collect any of this information (it's a prospective study, these are routine data!), or they didn't bother to report it.
When you call the description inadequate do you actually mean you feel they should have controlled for additional factors? That the description is perfectly adequate of the factors they were controlling for?
No. I mean exactly what I actually said. The fact that they also didn't control for anything meaningful is another but related point. I expanded on this in my original comment (which I thought you were replying to, apologies)
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u/Dry-Painter-9977 1d ago
It's most likely just the reuptake of X hormones from PTSD. Would love to see a study done with people who don't even know their family history in regards to the holocaust.
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u/bluewhale3030 1d ago
Reuptake? X hormones?
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u/Dry-Painter-9977 1d ago
When you feel an emotion your brain will recycle the neurotransmitters used and pre load them to the front of your brain, basically like muscle memory. Anti psychotics for example block the reuptake of dopamine to stop people getting over stimulated.
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u/neuro__atypical 21h ago
When you feel an emotion your brain will recycle the neurotransmitters
Your brain always recycles neurotransmitters. It has nothing to do with feeling an emotion. Your brain wouldn't work if it didn't recycle them. Some of them get put back into the synaptic vesicles, that's what reuptake is.
and pre load them to the front of your brain
???
Anti psychotics for example block the reuptake of dopamine
No, stimulants do that. That's what methylphenidate (Ritalin) does. It increases dopamine levels in the synapse. That would usually worsen psychosis.
to stop people getting over stimulated.
Psychosis has nothing to do with getting over stimulated. Antipsyhotics are D2 receptor antagonists, not dopamine reuptake inhibitors.
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u/thewooba 14h ago
Lil bro just stop. Reuptake of dopamine means it's getting vacuumed out of the synapse where it actually does something. This isn't the right sub for misinformation
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u/sometimeshiny 1d ago
Abstract
The transmission of trauma across generations, particularly among descendants of Holocaust survivors, presents a complex interplay of psychological and epigenetic adaptations. This study explored the long-term impacts of Holocaust trauma on the third and fourth generations, focusing on the quality of social-emotional ties and psychopathology, as well as the epigenetic variation in the oxytocin system, the Hypothalamic-Pituitary-Adrenal (HPA) stress axis, and the Sympathetic Nervous System (SNA). Involving 371 participants, including 186 third- and fourth-generation descendants of Holocaust survivors (54.8% women, mean age = 29.67), we employed DNA methylation analysis of saliva samples to uncover these dynamics. Our findings revealed that descendants exhibited significantly lower general attachment avoidance, and a DNA methylation pattern associated with stronger activation of the oxytocin system, indicating enhanced social bonding and social emotion regulation. Conversely, they showed distinct DNA methylation patterns in CRH, CRHBP, FKBP5, and NR3C1 genes linked to increased HPA axis activation and more pronounced stress reactivity. Despite the presence of these two DNA methylation patterns, no elevated levels of psychopathology were observed. Our results highlight the dual nature of trauma transmission, with descendants displaying both vulnerabilities and resilience. While stronger oxytocin system activation may support social cohesion and stress reduction, stronger HPA axis reactivity could ensure sustained vigilance and preparedness. Our findings thus underscore the intricate balance between genetic, epigenetic, and environmental factors in shaping resilience and offer insights into the potential for long-term growth following inherited trauma.
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u/reedmore 22h ago
First sentence reads like trauma transmission across generations is already an established fact.
Is there really a broad consensus on this?
What is the operational definition of trauma used here?
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u/IB_Yolked 22h ago
Probably the most famous/researched example is from The Dutch Hunger Winter during WW2
Persistent epigenetic differences associated with prenatal exposure to famine in humans - PMC https://share.google/Wml125JwMwAqIsXTK
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u/SaltZookeepergame691 12h ago edited 11h ago
That is direct exposure, though. The participants were in utero during the famine, and were (in general) severely growth restricted because their mothers were starving. The DNA methylation patterns observed are applied as a direct consequence of events during the lifecourse of the person.
No one is disputing these direct metabolic effects - they are easily reproducible in humans and mammals.
What is far, far more controversial are claims of transgenerational inheritance of some sort of stress, with no direct exposure, supposedly mediated by methylation markers. In animal models these findings are not consistent between papers, and the data in humans is really patchy (and often based on very limited papers, eg this one, or the one from a decade ago that basically kickstarted the whole field [now cited ~600 times, despite being widely criticised by (epi)geneticists!])
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u/SaltZookeepergame691 22h ago
If you read the paper and try to actually work out what they did, you'll be disappointed.
Take the control group. Who is it? How was it recruited? What are their characteristics? How do we know they are effective controls for the 'holocaust descendent' group? None of this is communicated, at all. This is basic.
On that note, let's examine the descendent group. Is it a single grandparent survivor? Either lineage? It wasn't verified, seemingly. They recruited people via targeted advertising with compensation. What do we know about them? Almost nothing.
There's adjustment only for age, sex, batch effects, and estimated cell proportions. They also state they control for adverse childhood experience in sensitivity analysis, but never describe how they measure this, or quantify it. No data on or control for genetic ancestry, smoking, BMI, alcohol, disease, SES/education, etc.
There's no multiplicity control, despite many, many tests being done.
They constantly talk about function, eg "While stronger oxytocin system activation may support social cohesion and stress reduction, stronger HPA axis reactivity could ensure sustained vigilance and preparedness." - this is completely hypothetical, not even based on RNA levels - it's purely extrapolated from methylation data that may or may not translate to gene/protein expression and function.
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u/turtleduck 21h ago
yeah I have no idea how they could control for something as complex as generational trauma from the Hocaust. anecdotally, from the Jewish POV, there's still a fuckton of trauma that we're still processing, and different parts of the diaspora's survivors settled in different parts of the world. I find it distasteful to call myself "resilient" because my ancestors were fortunate enough to make it out of a genocide. there's definitely some weird bias going on in this article
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u/MundaneChampion 21h ago
This is a joke right. They matched on age and sex, estimated saliva cell types, ran ComBat, tossed in couple as a random effect, and called it a day. There’s no serious adjustment for socioeconomic status, education, neighborhood, religiosity, migration history, or current stress load, I.e. variables that map directly onto both methylation and attachment.
Recruitment via social media and a paid knowledge-center gimmick biases a self-selected, educated, Israel-based couple sample. Then descendants are compared to “non-descendants” without geographically or socio‑demographically yoked controls. No household-level matching, no sibling/cousin designs, no community clustering, no sensitivity analyses for unmeasured confounding, and no negative controls. ACEs are waved around as the confounder du jour, while prenatal factors, parental psychopathology, and contemporaneous life events go unmeasured.
They use saliva methylation as a proxy for brain processes, don’t collect expression data, and then infer function. The model is overfit to lab artifacts and underfit to the real-world variables that would actually distinguish descendants from whoever answered a Facebook ad.
The difference in rigour between Nature, and the other open access journals in its portfolio is ASTOUNDING.
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u/ComprehensivePea2276 5h ago edited 4h ago
Completely agree. I would have hoped they would also throw in some PRS score to control for genetics vs. epigenetics as well.
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u/Nevesflow 23h ago edited 23h ago
But… wait…
Not to be racist or anything, but couldn’t this simply be attributed to these individuals being Ashkenazi Jews (so a specific population that managed to maintain a semblance of ethnical cohesion in multiple countries) in regions of the world where you couldn’t be anything but the descendant of an holocost survivor, if you were indeed a Jew ?
What’s the control group ? General population with no ethnic specificity ?
I’d be convinced if they found the same mutations among the descendants of other populations that have been genocided.
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u/tonicella_lineata 22h ago edited 22h ago
I haven't read the full study, but the abstract says "Holocaust survivors" - that's a lot more than just Ashkenazim. Other Jewish groups (like Sephardim and Mizrahim) were involved, as were groups like the Romani, disabled people, and queer folks. And even if the study is focused on Ashkenazim, not every single Ashkenazi person was in Europe at the time. Jews in the US were certainly not having a great time during WWII, of course, but if you're studying genetic trauma markers, "people in the US experiencing significant discrimination" is probably gonna give different results than "people who actively escaped a death camp in Europe."
I would also be interested to know exactly which groups were studied (both as the focus and the control), it's an important question to be sure. But there's no reason to assume right out the gate that they only studied Ashkenazim and only used non-Ashkenazim as the control, especially since this is far from the first study on epigenetic and generic variances in the descendants of trauma survivors. I'm not sure if they all show the same mechanisms (not quite my wheelhouse), but it would be pretty weird if this one variation, that's consistent with other findings on generational trauma, happened to simply be a trait of Ashkenazim.
(Edited to clarify a point and cite a couple of other studies that have been done)
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u/Nevesflow 13h ago edited 13h ago
"Other Jewish groups (like Sephardim and Mizrahim) were involved"
Obviously yes, but I was hinting at the fact that a vast portion of Ashkenzim in Europe were simply erased from the population and that their descendants were the most likely to be the ones studied here. I mean at least from what I understand.
"And even if the study is focused on Ashkenazim, not every single Ashkenazi person was in Europe at the time." Which is why I'd be curious to see what would happen if you'd do the same study on American jews for example.
"But there's no reason to assume right out the gate that they only studied Ashkenazim and only used non-Ashkenazim as the control"
Not only, but it's difficult to ignore a possible ehtnical bias in both groups, especially if you're gonna start studying the genome of a specific group of people...
"but it would be pretty weird if this one variation, that's consistent with other findings on generational trauma, happened to simply be a trait of Ashkenazim."
Not so weird that I'd completely rule it out though.
TL;DR : I'd really like to know if they have any data on their population sample beyond self reporting as "descendant of a holocaust survivor". Because I think even that term creates a social bias : if you're jewish, I'd wager you're simply more likely to perceive yourself as such and participate in a study that would potentially reinforce an already strongly ingrained identity narrative among your community.
Besides, not only did jews make up about 80 to 85% of the holocost victims (while disabled were around 2-3% and queer 1% or less), but I'd wager jews likely had way more descendants than queer people and disabled people, if you think about it for a second... No ?
And if you add the exponential effect of giving birth over three generations, I think you're setting yourself up for a very, very strong sample bias.
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u/ComprehensivePea2276 5h ago
They just sampled only Israeli couples and then asked them if they were or were not 3rd / 4th gen survivors of the Holocaust.
So it should be very /roughly/ apples to apples in terms of group ancestry, but to your point, there were no polygenic risk scores used to deconfound genetics from epigenetics -- which I imagine would be considered the norm for papers like this in more prestigious journals.
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u/NewlyNerfed 1d ago
Generational trauma is real. My gentile husband, who is a wonderful and empathetic ally, still just doesn’t see the world the way I do as someone with relatives who died in the Holocaust. I saw a comedian say that for Jewish people, the Holocaust is always just sort of hanging around over our heads, never fully going away.
I expect this comments section is going to devolve.
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u/Ambitious_Language62 1d ago
Generational trauma sucks. I’m half Navajo. We got some of that. Sucks to see that these conditions are still being created.
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u/NewlyNerfed 1d ago
You definitely get some of that, and I fully agree it’s a tragedy that it never ends.
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u/sometimeshiny 1d ago
It absolutely is and leads to outcomes where the offspring is primed to cortisol sensitivity. Cortisol increases glutamatergic throughput to neurons which over time and heightened delivery rate can lead to excitotoxicity and apoptosis/neuronal death. That means neurological disease.
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u/Nevesflow 13h ago
In that case, shouldn't we see similar effects in people who have a history of mental and physical abuse in their family, no ?
(Not saying we don't, actually curious if we do)
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u/sometimeshiny 8h ago
Yes we should, for sure.
Title Authors Year Childhood maltreatment and methylation of FK506 binding protein 5 gene (FKBP5) Tyrka et al. 2015 Early-Life Adversity–Induced Epigenetic Reprogramming of Prefrontal Cortex in Rats Subjected to Maternal Separation Francis et al. 2025 Impact of acute stress exposure on genome-wide DNA methylation Miller et al. 2025 Methylation of the FKBP5 gene in association with FKBP5 genotypes, childhood maltreatment and depression Klinger-König et al. 2019 There are also those regarding PTSD which would apply as well.
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u/Nevesflow 8h ago
Thank you.
And now I'm falling down the rabbit hole, learning that childhood trauma and PTSD may in fact worsen ADHD symptoms...
But I fear this kind of knowledge could be a bit of a double edged sword : is the relief of finding justification for your hardships in factors beyond your control worth the risk of eroding your self-accountability, and in the process, your potential for self-actualization ?
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u/sometimeshiny 8h ago
I understand your final sentence's view. My father was a combat wounded Vietnam veteran who took eight rounds and mortar shrapnel causing epigenetic AND genetic change in me. This was unrecognized by doctors and they diagnosed me with tendonitis as a child, which was incorrect. My father died of ALS in 2014. I have had prodromal ALS from birth which has progressed to being fully homebound and on track to go out like Hawking. But let me state, I am solving this disease with the information I am spreading to you and others. I think it is important that we reduce suffering where we can and that should be our general goal when looking towards advancement. Reduce suffering for others. So actualization lead to that ending for me. Solve these things for you all before I die off from it.
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u/Arnoski 13h ago
Generational trauma is awful. I’m Japanese and indigenous, and my ancestors were at war for hundreds of years. Between that and the persecution that followed certain changes of government, my body lights up like a Christmas tree around certain stress events that do nothing to other people.
Immense resilience in the moment. Afterwards, they come down is awful.
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u/Not_a_N_Korean_Spy 21h ago
Does devolve mean other people taking about other generational traumas? That should be ok, shouldn't it?
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u/NewlyNerfed 20h ago
Oh, no, of course that’s all right! I meant I knew someone was going to come at me with Palestine and indeed they did.
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u/TasteofPaste 1d ago
What do you think the generational trauma is going to look like for the Palestinian people, the ones who manage to survive ethnic cleansing currently taking place in Gaza?
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u/NorthernDevil 22h ago
Probably extremely similar across victims of various instances of genocide. But the fact that you are bringing this up to a random Jewish person unaffiliated with the state of Israel is fucked.
Especially so considering you made this comment on a post about the generational trauma of a genocide motivated by religious bigotry.
Really reinforces OP’s point…
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u/bluewhale3030 1d ago
Why do you think it's ok to ask a random person this just because they're Jewish? The average Jewish person has nothing to do with the actions of the Israeli government. Jewish people as a whole are not responsible for the actions of a country that most of them have no actual connection with.
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u/fractalife 1d ago
Worded a different way, it could be a sense of camaraderie and compassion for one another. The conditions that create these adaptations are not unique to either event.
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u/The_grope_gatsby 1d ago
Don’t need to word it a different way. Could bring up the Uyghurs, Sudan, Armenians etc as well.
But because Jewish…..
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u/AffectionateTitle 23h ago edited 23h ago
Not sure, perhaps like many genocide survivors their trauma will probably coupled with a hope they won’t be used as pawns in Internet forums to drive further bigotry.
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u/NewlyNerfed 1d ago
I don’t engage with strangers about Palestine other than to say I’m not a Zionist. Enjoy your day.
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u/Commercial_Height645 20h ago
When a nation is created as a Jewish homeland, settled by Jewish colonisers and to this day maintains strong influence among Jewish communities world-wide. It's fair to assume it speaks for Jewish people. Not entirely correct. But a fair assumption. Unfortunately, a large part of holocaust studies, particularly modern holocaust scholarship, does serve a political/ideological goal for modern Israel. Hence why they fund so much of it.
It's been politically important to make the holocaust a Jewish event whilst marginalising the many Roma, queer and disabled people, five million gentile Poles, etc. It's a very difficult subject to address because the sheer suffering, particularly that felt by Jewish people, is so astronomical, but also one that academically, should not be disconnected from the power structures it is now part of.
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u/NoWealth1512 22h ago
It was the worst crime in history and it wasn't that long ago. I don't think you have to be Jewish to understand that, but obviously if you're Jewish it's more personal.
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u/imspecial-soareyou 22h ago
This isn’t new territory. It has been studied already.
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u/percahlia 22h ago
the OP believes they’re being controlled by aliens and keeps posting research about trauma being genetic. i have a slight feeling they’re trying to blame any kind of external factor for their issues. it’s really easy to tell what post here is posted by the same person.
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u/turtleduck 21h ago
their bio says their "work" directly refutes Darwin's theory of random mutations, so yeah, take this one with a pillar of salt
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u/Big-Fill-4250 22h ago
I mean, this could also mean that jewish folks more atuned to being open and close to others survived the awfulness that was the holocaust
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u/Not_a_N_Korean_Spy 21h ago
There is another group of people they can try to eventually replicate the results with:
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