This paper is a PR gold mine but a methodological disaster, which is par for the course in "EWAS" (epigenome-wide association studies). At one point I had to remind a coauthor that pointing out structural problems in fashionable studies such as these is a quick way to lose (more) faith in modern peer review; for some reason she thought that EWAS enthusiasts gave a flying crap whether the "genes" they were studying were subject to structural variation (e.g. amplification and deletion). Ha! Ha! Ha!
Anyways. Their functional enrichment analysis is uncorrected for the known bias of the platform (something that has been repeatedly addressed by multiple authors since 2012), and no attempt appears to have been made to correct for cryptic stratification (i.e. structural polymorphisms, which are rampant in human populations, and particularly among so-called metabolic genes), though in the study population that may not be a major issue.
Quantile normalization is only appropriate if one can reasonably assert that the overall distribution of measurements is roughly the same between individuals and groups; this assumption has been shown to be invalid in the absence of positive and negative controls for gene expression, whence its original propagation, and more so for DNA methylation under various conditions. The batch correction approach used here is notorious for squashing real signal, although paradoxically that may have moderated some of the other methods choices.
Moreover, the paper demonstrates that a particular sample of high-SES vs. low-SES individuals in Cebu in the Philippines demonstrates some (fairly tiny) differences in DNA methylation at a relatively small number of CpGs (about 2000 out of 485000 or so measured and 110000 or so tested), without particular note as to whether the sites are clustered, functional, or otherwise of interest. The functional impact of these changes are difficult to interpret, partly because of the bias in the functional analysis (something that has been established for nearly a decade; the authors clearly went shopping for methods in a "confirmatory" style).
We shan't even bother to discuss the effect of [mal]nutrition on metabolism and thereby upon DNA methylation and cell composition (both intertwined, although an attempt was made to correct for the interaction), which further muddies the waters w/r/t SES as opposed to individual-level effects. The analysis is done with a fixed-effects model assuming unstructured shrinkage, which of course is a bit odd considering that the measurements have a relatively easily determined correlation structure (their sample size is sufficient to estimate this) and thus variance decomposition could have been highly informative. This is doubly odd for a population "epigenetics" study, given that variance components were literally invented in population genetics.
In conclusion, while it's a lovely piece for a PR department, the actual relevance of either the measurements or the phenomena to actual humans and public policy is quite difficult to interpret. Perhaps that was the point...
> socioeconomic status (SES) is a powerful determinant of human health and disease, and social inequality is a ubiquitous stressor for human populations globally
It is common to see why this could be a big problem for poor people as they have to worry about health, food, etc for day to day living while we take them as granted and can focus on other things like writing code, going to meetings, and the like without worrying about where the next meal is going to come from!
My observations is that our society puts too much emphasis on having people prove they are self-reliant, instead of improving its population's productivity. In this dichotomy, the former is detrimental to the society, the latter would enhance it.
I think focusing on productivity would go further than the dichotomy's of "welfare or not", where people are mostly skeptical of whether a subsidized poor person is contributing to society with taxpayer's money.
Relegating the role of governance to productivity allows even prisoner rehabilitation to change. It allows jailable offenses to be viewed under the lens of whether this is useful to the productivity of society, instead of simply punishing someone.
Everyone who wrote and authorized this press release ought to be fired. The paper offers no evidence of relevance to epigenetic inheritance, and has nothing to do with nature vs. nurture.
All that's going on here is that people in the Philipenes have differences in environmental exposures that affect gene expression in their immune system, and this, unsurprisingly, differs by SES. No evidence that any of these marks are more than temporary marks of current gene expression patterns let alone anything as shocking as passing through the germ line to the next generation.
> We did not find support for the hypothesis that low childhood SES would be associated with DNAm in young adulthood, independent of current SES. Prior research has reported sensitive periods of SES influence (Borghol et al., 2012; Lam et al., 2012), but our study is likely under-powered to test for this effect.
>understandings of genes as immutable features of biology that are fixed at conception
This 'understanding' has been known to be wrong for 30+ years now. Rearrangements, microchimerism, epigenetics, chromosome organization etc. are all things that exist and modulate information transfer beyond the standard four letters or the 'environment' (whatever people think it means) and we're still only scratching the surface. I keep saying it and I'll say it again: DNA is not source code, your genes are not initial character stats in a video game. That's not how any of this works and it frustrates me whenever I read otherwise smart people making arguments that rely on premises originating from a high schooler's (or 1970's) understanding of genetics. It's even worse when the dreaded 'nature/nuture' gets mentioned.
My, admittedly weak, understanding is that the analogy is (much) more apt than not. Sure, the means by which that code is 'compiled' and 'executed' is much different than in the computers we've built, but, for one, DNA, genes, chromosomes, and all of the other various levels of organization of those units of information seem to be remarkably, amazingly stable, for many (most? almost all?) organisms, which seems to strongly imply that 'DNA is source code' is about as true as 'Earth is a sphere'. Sure, they're both only approximately true, but how approximately they're true (or not) is very important. Asimov explained this extremely well:
What epigenetics is not is anything like Lamarckian inheritance, at least not at all to the same degree.
> Rearrangements, microchimerism, epigenetics, chromosome organization etc. are all things that exist and modulate information transfer beyond the standard four letters or the 'environment' (whatever people think it means) and we're still only scratching the surface.
Sure, but that doesn't mean that the central dogma of biology is entirely wrong, just that it's not always and everywhere true exactly. The current best understanding of epigenetics (quoted from my second link above) is that, whatever it is, it is such that:
> very little of [genetic] inheritance is perturbed by epigenetic effects
I still don't buy the "There is no nature vs. nurture" statement. Maybe there's more than nature vs. nurture, or more complicated than nature vs. nurture. But totally no nature vs. nurture? Overstatement.
Genes do explain much of the variation between people for many characteristics. You can think of them as initial character stats that are then modified by environmental factors and random noise.
[+] [-] apathy|6 years ago|reply
Anyways. Their functional enrichment analysis is uncorrected for the known bias of the platform (something that has been repeatedly addressed by multiple authors since 2012), and no attempt appears to have been made to correct for cryptic stratification (i.e. structural polymorphisms, which are rampant in human populations, and particularly among so-called metabolic genes), though in the study population that may not be a major issue.
Quantile normalization is only appropriate if one can reasonably assert that the overall distribution of measurements is roughly the same between individuals and groups; this assumption has been shown to be invalid in the absence of positive and negative controls for gene expression, whence its original propagation, and more so for DNA methylation under various conditions. The batch correction approach used here is notorious for squashing real signal, although paradoxically that may have moderated some of the other methods choices.
Moreover, the paper demonstrates that a particular sample of high-SES vs. low-SES individuals in Cebu in the Philippines demonstrates some (fairly tiny) differences in DNA methylation at a relatively small number of CpGs (about 2000 out of 485000 or so measured and 110000 or so tested), without particular note as to whether the sites are clustered, functional, or otherwise of interest. The functional impact of these changes are difficult to interpret, partly because of the bias in the functional analysis (something that has been established for nearly a decade; the authors clearly went shopping for methods in a "confirmatory" style).
We shan't even bother to discuss the effect of [mal]nutrition on metabolism and thereby upon DNA methylation and cell composition (both intertwined, although an attempt was made to correct for the interaction), which further muddies the waters w/r/t SES as opposed to individual-level effects. The analysis is done with a fixed-effects model assuming unstructured shrinkage, which of course is a bit odd considering that the measurements have a relatively easily determined correlation structure (their sample size is sufficient to estimate this) and thus variance decomposition could have been highly informative. This is doubly odd for a population "epigenetics" study, given that variance components were literally invented in population genetics.
In conclusion, while it's a lovely piece for a PR department, the actual relevance of either the measurements or the phenomena to actual humans and public policy is quite difficult to interpret. Perhaps that was the point...
[+] [-] vipref|6 years ago|reply
It is common to see why this could be a big problem for poor people as they have to worry about health, food, etc for day to day living while we take them as granted and can focus on other things like writing code, going to meetings, and the like without worrying about where the next meal is going to come from!
[+] [-] rolltiide|6 years ago|reply
I think focusing on productivity would go further than the dichotomy's of "welfare or not", where people are mostly skeptical of whether a subsidized poor person is contributing to society with taxpayer's money.
Relegating the role of governance to productivity allows even prisoner rehabilitation to change. It allows jailable offenses to be viewed under the lens of whether this is useful to the productivity of society, instead of simply punishing someone.
[+] [-] unknown|6 years ago|reply
[deleted]
[+] [-] azeotropic|6 years ago|reply
All that's going on here is that people in the Philipenes have differences in environmental exposures that affect gene expression in their immune system, and this, unsurprisingly, differs by SES. No evidence that any of these marks are more than temporary marks of current gene expression patterns let alone anything as shocking as passing through the germ line to the next generation.
[+] [-] KenanSulayman|6 years ago|reply
[+] [-] aluren|6 years ago|reply
This 'understanding' has been known to be wrong for 30+ years now. Rearrangements, microchimerism, epigenetics, chromosome organization etc. are all things that exist and modulate information transfer beyond the standard four letters or the 'environment' (whatever people think it means) and we're still only scratching the surface. I keep saying it and I'll say it again: DNA is not source code, your genes are not initial character stats in a video game. That's not how any of this works and it frustrates me whenever I read otherwise smart people making arguments that rely on premises originating from a high schooler's (or 1970's) understanding of genetics. It's even worse when the dreaded 'nature/nuture' gets mentioned.
[+] [-] aeorgnoieang|6 years ago|reply
My, admittedly weak, understanding is that the analogy is (much) more apt than not. Sure, the means by which that code is 'compiled' and 'executed' is much different than in the computers we've built, but, for one, DNA, genes, chromosomes, and all of the other various levels of organization of those units of information seem to be remarkably, amazingly stable, for many (most? almost all?) organisms, which seems to strongly imply that 'DNA is source code' is about as true as 'Earth is a sphere'. Sure, they're both only approximately true, but how approximately they're true (or not) is very important. Asimov explained this extremely well:
- [Asimov - The Relativity of Wrong](http://chem.tufts.edu/answersinscience/relativityofwrong.htm)
'Epigenetics' itself seems like it might not be a particular thing among different people:
- [The misunderstanding of epigenetics – Insitome](https://blog.insito.me/the-misunderstanding-of-epigenetics-a...)
What epigenetics is not is anything like Lamarckian inheritance, at least not at all to the same degree.
> Rearrangements, microchimerism, epigenetics, chromosome organization etc. are all things that exist and modulate information transfer beyond the standard four letters or the 'environment' (whatever people think it means) and we're still only scratching the surface.
Sure, but that doesn't mean that the central dogma of biology is entirely wrong, just that it's not always and everywhere true exactly. The current best understanding of epigenetics (quoted from my second link above) is that, whatever it is, it is such that:
> very little of [genetic] inheritance is perturbed by epigenetic effects
[+] [-] educationdata|6 years ago|reply
[+] [-] heavenlyblue|6 years ago|reply
It is source code, it's just that source code is self-modifying.
[+] [-] BearsAreCool|6 years ago|reply
[+] [-] johnchristopher|6 years ago|reply
[+] [-] reasonaway|6 years ago|reply
[+] [-] conse_lad|6 years ago|reply
[+] [-] dang|6 years ago|reply
It's good to share links to previous threads, but only if there's actually a discussion there.
[+] [-] Cynddl|6 years ago|reply
[+] [-] sci-hub|6 years ago|reply
[+] [-] dang|6 years ago|reply