
Poverty leaves a mark on our genes - howrude
https://www.eurekalert.org/pub_releases/2019-04/nu-pla040419.php
======
apathy
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...

------
vipref
> 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!

~~~
rolltiide
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.

~~~
ta1234567890
I agree with the sentiment of changing the narrative, but productivity seems
to already be a big part of western society and it seems pretty soul-less. Why
not focus on well-being of everyone?

~~~
rolltiide
> Why not focus on well-being of everyone?

Because that won't gain consensus.

But demonstrating how some parts of our culture undermine productivity can.

I think we could reach similar outcomes, if the lack of well-being can be
proven to show that it undermines productivity.

~~~
wallace_f
I'm not sure what fraction of _paid_ jobs even contribute greater than their
cost to society. The War on Poverty has spent trillions, and poverty has
_increased._ A lot of industries obviously don't contribute (tax attorneys,
lobbyists, bureaucrats, administrators (see the Rise of the Administrator in
healthcare), even much of law enforcement, academia, or regulators). Actually
even my first high-paid job working for a financial tech company, I'm
convinced didn't contribute to society. Most of our work was mandated by
regulatory laws, and most of our customers were capture by monopolistic
competition or downright aggressive, questionable sales.

I don't see anyone saying this, but I think fixing the bottom 10% of society
requires fixing the top 90%. I see no way that happens. Nobody accepts blame
for being wrong, and most people's cognitive capabilities are filled by an
evening watching cable TV.

~~~
rolltiide
I don't agree on that being the immediate issue.

The bottom with disruptions to their income are detrimental to society’s
health. Public sector monetary solutions are untolerated and private sector
solutions of employment are often inaccessible or inadequate. We can address
their productivity.

~~~
wallace_f
It's not the problem for those that can't work--the truly disabled--but I
think it is for those who can. They're not inherently incapable of being
productive.

------
azeotropic
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.

~~~
KenanSulayman
> 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.

------
aluren
>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.

~~~
heavenlyblue
>> DNA is not source code

It is source code, it's just that source code is self-modifying.

~~~
aluren
Also the compiler is self-modifying. And the compiler flags as well. And the
OS. And the chip architecture sometimes. Like, at what point do we decide that
pushing the analogy further is just silly and just drop it altogether?

~~~
mannykannot
And yet something guides the human zygote in developing as a human. At what
point do we stop focusing on refuting simplistic ideas and turn our attention
to what is now known?

~~~
aluren
That 'something' you mention is called _developmental biology_ and it's yet
another level of abstraction removed from the basic cell machinery that
operates around DNA. It also has nothing to do with compilers or anything
computer related. At some point the analogy is just more harmful than anything
else.

------
conse_lad
Same story shared one day ago.
[https://news.ycombinator.com/item?id=20190233](https://news.ycombinator.com/item?id=20190233)

~~~
dang
Reposts are fine if a story hasn't had significant attention yet:
[https://news.ycombinator.com/newsfaq.html](https://news.ycombinator.com/newsfaq.html).

It's good to share links to previous threads, but only if there's actually a
discussion there.

------
sci-hub
Link to paper [PDF]: [http://sci-hub.now.sh/go/10.1002/ajpa.23800](http://sci-
hub.now.sh/go/10.1002/ajpa.23800)

~~~
dang
It's fine to provide the occasional link but please don't do special-purpose
accounts on HN.

