6 ms·

Bzzt. Nope. Epigenetics is heritable as are child-rearing practices and this is a cross-sectional design, not longitudinal. (Not even within-family comparisons!

by gwern 9y ago

Bzzt. Nope. Epigenetics is heritable as are child-rearing practices and this is a cross-sectional design, not longitudinal. (Not even within-family comparisons!) For all they know, those epigenetic differences were present from birth, as is often the case. Yet another epigenetics study whose overhyped causal claims are dead on arrival.

deleted 9y ago
[deleted]
plidner 9y ago
Handily dismissed by a hypothesis conceived in a moment with zero effort. Between the cell's nucleus, where complex enzymes transcribe to RNA in a chemical process, resulting in gene expression, that concludes with the construction of proteins, your claim is that high stress at early developmental moments, not only has no long term effect, but no effect at all? It sounds like you've conducted a study. Is your sample size N=1 where 1 equals you?
- deleted 9y ago
  [deleted]
- saurik 9y ago
  This person is not claiming to know a cause: this person is claiming that there is another hypothesis that you can conceive "in a moment with zero effort" that this study design was incpaable of isolating. There are multiple reasons that could have happened: one is that the scientists didn't think of it (which to me would undermine their credibility as it is really obvious as a possibility), a second is that this study was much cheaper and they weren't sure there would be a correlation at all (so now there is enough evidence to warrant a better study), and a third is that they didn't care about "why" and were only interested in "that". To the scientist's credit, the article quotes them as saying that they don't know the cause, which is great, and they say "too early" so they might intend to keep going. To their discredit, they gave enough of an explanation based on stuff they weren't sure of to the reporter to guide it to the point where the headline is just guesswork, not real science. On the other hand, you certainly... and apparently the scientists :/... are simply assuming your explanation and then using a study that is incapable of discerning the the difference between these two hypotheses to dismiss the idea, which is clearly not OK. [I am sorry if someone saw a draft of this comment or if it appeared under the wrong parent for a moment: I was having issues replying on my iPhone today :/.]
  - SubiculumCode 9y ago
    In my own work, reporters of my research off end up bending thing to say something kind of stupid, and definitely not what I had said.
- gwern 9y ago
  > Handily dismissed by a hypothesis conceived in a moment with zero effort. Not at all. What I am saying is a standard criticism of overhyped epigenetics studies which follows from the lazy design which does not control for very large known confounds (pretty much all effects are smaller in a within-family comparison) or actually demonstrate it's not reverse causation, which as in OP results in such wild overhyping of causal implications. This is as much 'zero effort' as noting, of the latest nutrition study claiming that fat (or carbs, or red meat, or protein, or milk, or eggs, or...) will definitely kill you, that the methods simply do not work for what they are claimed to prove. If you find the criticisms tiresomely cliche & predictable, that's an indictment of the researchers or funders, not the criticisms. (I know I find it tiresome to point out the same problems every time and respond to comments shocked that correlation!=causation, or that most human traits are heritable, or that p-values mean nothing interesting, estimates are inflated by publication bias, one shouldn't control for intermediate variables, gains fade out etc. I suppose I do it out of stubborn perversity. I keep resolving not to get into arguments about these things, and keep failing.) It has been demonstrated many times that epigenetics are heritable, affected by gene-environment correlations, and are not themselves causal for many outcomes they have been claimed to be but passive indicators of environment; so OP is, at best, possible but not probable and the speculation that the epigenetics changes will have any causal effects later on to be taken with considerable skepticism... (as they are more likely to simply indicate the manifestation of the childrens' genes as inherited from their parents). Epigenetics is of tremendous biological interest as it is often how genetics exerts its effects, but unfortunately, that's not what people want epigenetics to be. You may remember the scientific reaction to Siddhartha Mukherjee's New Yorker article on epigenetics last year which similarly took likely-confounded & reverse causation epigenetics claims at face value.
phkahler 9y ago
My thought was that there are lots of variations and they just found a coincidence that will require a followup experiment to replicate and rule out chance. Your points are valid as well - if you're claiming a change, you gotta show the before and after.
seccess 9y ago
This paper seems to indicate there is a causal relationship, at least in rats (I'm getting this from someone who knows more, not an expert myself): https://www.biorxiv.org/content/early/2017/11/03/191791 https://www.biorxiv.org/content/early/2017/11/03/191791
jlg23 9y ago
Quoting some sources would help a) my understanding and therefore b) your claims.
deleted 9y ago
[deleted]
SubiculumCode 9y ago
While you raise valid limitations of the study, those limitations do not provide a valid cuse to dismiss the result outright. Random assignment to different levels of "cuddles" in humans is probably not ethical,and longitudinal studies are expensive. To get a grant funding a longitudinal study you usually have to have a) animal model based evidence from the literature b)have already demonstrated in humans the phenomenon cross-sectionally. As a side note, your comment would have been perfectly reasonable sounding if you had left off the first two words, and the last sentence. But you didn't.
- gwern 9y ago
  None of that is true. We have a long history of epigenetics studies which let us known this is almost certainly yet another failure. Random assignment is not unethical under many designs (exercise for the reader: think of one. Hint: draw inspiration from economics), is not necessary to improve over what they did, and longitudinal designs at their simplest merely require two sampling periods. It is also untrue that you 'usually' have to have demonstrated it in animals or cross-sectionally because many longitudinal studies are convenience samples, record-based or population registries, or collect large numbers of measurements to see what comes out in later analyses of things they hadn't thought of before.
  - SubiculumCode 9y ago
    Clearly I was not claiming that random assignment is un ethical generally, but specifically in the case of assigning the degree of physical affection/cuddling to a baby is probably unethical. As someone who has been involved in multiple longitudinal studies, although not in epigenetics, I can say that they are more expensive. In terms of what I said about prior evidence, I was coming from a cognitive psych background where we do not typically deal with record-based data. We deal with participants directly. It is expensive and time consuming. Longitudinal studies usually follow cross-sectional evidence.
    - gwern 9y ago
      > but specifically in the case of assigning the degree of physical affection/cuddling to a baby is probably unethical. Alright, since you refuse to think, I'll give it to you for free: do an intent-to-treat design with incentives for additional cuddling for either the parents or hired helpers like nannies, or passive controls; as no infant receives less physical affection than they would otherwise, no one is hurt by the randomization and it is not unethical, but you still get a causal effect. (Not all of them will use it, and the ones who do, the difference will be smaller than if you could remove cuddling, but that's merely a matter of power.) Such designs are often used in economics, and are applicable to many topics where randomization is considered infeasible for 'ethical' reasons: if you have a limited supply of X, it can be allocated by lottery; if you want to measure the impact of health insurance, surely this is unethical? How could you ever study it? But no, you have limited Medicare funds, so you simply allocate by lottery. Charter schools, lead poisoning, vaccines, basic incomes, daycare, enrichment programs, cuddle subsidies etc. The winners get the additional treatment while the losers serve as baseline controls, finessing the ethical problems. As it is usually the case that there's not enough money to deliver the claimed-beneficial intervention to all possible beneficiaries, it's quite a general strategy. > As someone who has been involved in multiple longitudinal studies, although not in epigenetics, I can say that they are more expensive. I didn't say that they weren't, just that they were only somewhat more expensive, and they can be done cheaply in a number of ways. There are considerable economies of scale in these things - look at the UK Biobank.
deleted 9y ago
[deleted]
alehul 9y ago
Epigenetic tags are inheritable, yes, but when they're expressed and to what extent the epigenetic tags are expressed changes between individuals. Since expression of these tags result from external influences, I don't see what the relevance is. Can you explain? How does inheritance of these epigenetic tags, unexpressed, contradict the article?

by gwern 9y ago

deleted 9y ago

[deleted]

plidner 9y ago

Handily dismissed by a hypothesis conceived in a moment with zero effort. Between the cell's nucleus, where complex enzymes transcribe to RNA in a chemical process, resulting in gene expression, that concludes with the construction of proteins, your claim is that high stress at early developmental moments, not only has no long term effect, but no effect at all? It sounds like you've conducted a study. Is your sample size N=1 where 1 equals you?

deleted 9y ago
[deleted]
saurik 9y ago
This person is not claiming to know a cause: this person is claiming that there is another hypothesis that you can conceive "in a moment with zero effort" that this study design was incpaable of isolating. There are multiple reasons that could have happened: one is that the scientists didn't think of it (which to me would undermine their credibility as it is really obvious as a possibility), a second is that this study was much cheaper and they weren't sure there would be a correlation at all (so now there is enough evidence to warrant a better study), and a third is that they didn't care about "why" and were only interested in "that". To the scientist's credit, the article quotes them as saying that they don't know the cause, which is great, and they say "too early" so they might intend to keep going. To their discredit, they gave enough of an explanation based on stuff they weren't sure of to the reporter to guide it to the point where the headline is just guesswork, not real science. On the other hand, you certainly... and apparently the scientists :/... are simply assuming your explanation and then using a study that is incapable of discerning the the difference between these two hypotheses to dismiss the idea, which is clearly not OK. [I am sorry if someone saw a draft of this comment or if it appeared under the wrong parent for a moment: I was having issues replying on my iPhone today :/.]
- SubiculumCode 9y ago
  In my own work, reporters of my research off end up bending thing to say something kind of stupid, and definitely not what I had said.
gwern 9y ago
> Handily dismissed by a hypothesis conceived in a moment with zero effort. Not at all. What I am saying is a standard criticism of overhyped epigenetics studies which follows from the lazy design which does not control for very large known confounds (pretty much all effects are smaller in a within-family comparison) or actually demonstrate it's not reverse causation, which as in OP results in such wild overhyping of causal implications. This is as much 'zero effort' as noting, of the latest nutrition study claiming that fat (or carbs, or red meat, or protein, or milk, or eggs, or...) will definitely kill you, that the methods simply do not work for what they are claimed to prove. If you find the criticisms tiresomely cliche & predictable, that's an indictment of the researchers or funders, not the criticisms. (I know I find it tiresome to point out the same problems every time and respond to comments shocked that correlation!=causation, or that most human traits are heritable, or that p-values mean nothing interesting, estimates are inflated by publication bias, one shouldn't control for intermediate variables, gains fade out etc. I suppose I do it out of stubborn perversity. I keep resolving not to get into arguments about these things, and keep failing.) It has been demonstrated many times that epigenetics are heritable, affected by gene-environment correlations, and are not themselves causal for many outcomes they have been claimed to be but passive indicators of environment; so OP is, at best, possible but not probable and the speculation that the epigenetics changes will have any causal effects later on to be taken with considerable skepticism... (as they are more likely to simply indicate the manifestation of the childrens' genes as inherited from their parents). Epigenetics is of tremendous biological interest as it is often how genetics exerts its effects, but unfortunately, that's not what people want epigenetics to be. You may remember the scientific reaction to Siddhartha Mukherjee's New Yorker article on epigenetics last year which similarly took likely-confounded & reverse causation epigenetics claims at face value.

phkahler 9y ago

My thought was that there are lots of variations and they just found a coincidence that will require a followup experiment to replicate and rule out chance. Your points are valid as well - if you're claiming a change, you gotta show the before and after.

seccess 9y ago

This paper seems to indicate there is a causal relationship, at least in rats (I'm getting this from someone who knows more, not an expert myself): https://www.biorxiv.org/content/early/2017/11/03/191791 https://www.biorxiv.org/content/early/2017/11/03/191791

jlg23 9y ago

Quoting some sources would help a) my understanding and therefore b) your claims.

deleted 9y ago

[deleted]

SubiculumCode 9y ago

While you raise valid limitations of the study, those limitations do not provide a valid cuse to dismiss the result outright. Random assignment to different levels of "cuddles" in humans is probably not ethical,and longitudinal studies are expensive. To get a grant funding a longitudinal study you usually have to have a) animal model based evidence from the literature b)have already demonstrated in humans the phenomenon cross-sectionally. As a side note, your comment would have been perfectly reasonable sounding if you had left off the first two words, and the last sentence. But you didn't.

gwern 9y ago
None of that is true. We have a long history of epigenetics studies which let us known this is almost certainly yet another failure. Random assignment is not unethical under many designs (exercise for the reader: think of one. Hint: draw inspiration from economics), is not necessary to improve over what they did, and longitudinal designs at their simplest merely require two sampling periods. It is also untrue that you 'usually' have to have demonstrated it in animals or cross-sectionally because many longitudinal studies are convenience samples, record-based or population registries, or collect large numbers of measurements to see what comes out in later analyses of things they hadn't thought of before.
- SubiculumCode 9y ago
  Clearly I was not claiming that random assignment is un ethical generally, but specifically in the case of assigning the degree of physical affection/cuddling to a baby is probably unethical. As someone who has been involved in multiple longitudinal studies, although not in epigenetics, I can say that they are more expensive. In terms of what I said about prior evidence, I was coming from a cognitive psych background where we do not typically deal with record-based data. We deal with participants directly. It is expensive and time consuming. Longitudinal studies usually follow cross-sectional evidence.
  - gwern 9y ago
    > but specifically in the case of assigning the degree of physical affection/cuddling to a baby is probably unethical. Alright, since you refuse to think, I'll give it to you for free: do an intent-to-treat design with incentives for additional cuddling for either the parents or hired helpers like nannies, or passive controls; as no infant receives less physical affection than they would otherwise, no one is hurt by the randomization and it is not unethical, but you still get a causal effect. (Not all of them will use it, and the ones who do, the difference will be smaller than if you could remove cuddling, but that's merely a matter of power.) Such designs are often used in economics, and are applicable to many topics where randomization is considered infeasible for 'ethical' reasons: if you have a limited supply of X, it can be allocated by lottery; if you want to measure the impact of health insurance, surely this is unethical? How could you ever study it? But no, you have limited Medicare funds, so you simply allocate by lottery. Charter schools, lead poisoning, vaccines, basic incomes, daycare, enrichment programs, cuddle subsidies etc. The winners get the additional treatment while the losers serve as baseline controls, finessing the ethical problems. As it is usually the case that there's not enough money to deliver the claimed-beneficial intervention to all possible beneficiaries, it's quite a general strategy. > As someone who has been involved in multiple longitudinal studies, although not in epigenetics, I can say that they are more expensive. I didn't say that they weren't, just that they were only somewhat more expensive, and they can be done cheaply in a number of ways. There are considerable economies of scale in these things - look at the UK Biobank.

deleted 9y ago

[deleted]

alehul 9y ago

Epigenetic tags are inheritable, yes, but when they're expressed and to what extent the epigenetic tags are expressed changes between individuals. Since expression of these tags result from external influences, I don't see what the relevance is. Can you explain? How does inheritance of these epigenetic tags, unexpressed, contradict the article?