

The looming crisis in human genetics - rms
http://www.economist.com/displaystory.cfm?story_id=14742737

======
Estragon
I work in this field. The reasons for these problems are probably relatively
simple.

1) Current GWASs focus on common variants, but the population explosion over
the last few thousand years means it's likely that most human genetic
diversity is rare.

2) Current GWASs focus on the marginal effects of variation at single-
nucleotide sites, but it's likely that there are complex interactions between
different variations.

These misplaced foci of current GWASs have more to do with what we _could_ do
with current technology than with what we _ought_ to do, given these
biological realities: sequencing was so expensive that it was hard to
determine the rare variants; sample sizes were so small that we had to use
simplifying statistical assumptions like independent phenotypic effects from
each nucleotide variation. Those technological limitations are changing, now.

The "thoughtful geneticists" the article refers to aren't just wringing their
hands about this. They are working on both of these issues. (I'm one of them.)

~~~
narag
I'm very confused by the article. Not sure if it's because the language or
because it's not very clear. On the one hand it says that there are too little
evidence of "hereditability" to be useful to cure diseases. On the other hand
it says that there is a lot of evidence, to the point of being "disturbing",
of racial traits. What am I reading wrong?

~~~
carbocation
Regarding the missing heritability, they are claiming that this is a
deficiency of GWAS. It then goes on to talk about sequencing, which it says
_will_ find lots of evidence for miscegenation, etc. (To which I say, sure,
but what of it?)

In case you are not familiar with the methods, the difference between GWAS/SNP
analysis and sequencing is this: GWAS relies on surveying ~500,000 (up to 6
million now, but it doesn't really matter) known single nucleotide
polymorphisms. So you might ask, "which nucleotides of this subset of the
human genome differ in a systematic way between cases and controls."

With sequencing, you are surveying all nucleotides, not just a subset of
500,000. So you instead ask "which nucleotides out of the 3 billion (haploid)
differ between cases and controls?"

~~~
narag
_...will find lots of evidence for miscegenation, etc. (To which I say, sure,
but what of it?)_

Thank you for the explanation. I'd love to know more about my DNA, specially
if it says that I have a lot of far relatives around the world, I can't
understand that's a problem.

------
araneae
The central problem is that people don't understand what "heritable" or
"genetic" really means. Every trait you can possibly think of has a genetic
basis. I.e. having green hair is heritable, because people who dye their hair
funny colors are more likely to be risk takers, and those personality traits
are more likely in people with a higher fraction with such-and-such
neurotransmitter receptors, and the number of those receptors is influenced by
some gene by a few percentage points.

Just because it's genetic doesn't mean it's meaningful, anymore than it's
really meaningful to say that this mutation which means you have 1% more of x
receptor makes you go out and dye your hair green. It's ridiculous, and that's
the kind of relationship that all these genes have with pretty much all
phenotypes. The reason the effects are so small is because what the gene does
is so far removed and from whatever phenotype you're studying. (usually)

~~~
goodside
'The central problem is that people don't understand what "heritable" or
"genetic" really means.'

Apparently so. Heritability does not mean genetic causation. Language is
_extremely_ heritable (that is, children almost always speak the same language
as their parents), and not because there's a long just-so chain of genetic and
hormone events that ends in an innate facility for Cantonese.

~~~
gort
"Heritability" means something like "how much of the variation in a population
is due to genetic differences". This leads to some odd results, e.g. number of
arms has low heritability (almost all variation is due to environment).

Anyway, language is not heritable. The variation in the languages people speak
in a population is not due to genes but rather to environmental effects.

~~~
goodside
This is right. Readers, please mod down my comment above for being
simultaneously snarky and dead wrong.

------
lunchbox
The author's thesis statement is the following:

 _"The new genetics will reveal much less than hoped about how to cure
disease, and much more than feared about human evolution and inequality,
including genetic differences between classes, ethnicities and races."_

This thesis is revisited in the section on whole genome sequencing:

 _"The trouble is, the resequencing data will reveal much more about human
evolutionary history and ethnic differences than they will about disease
genes."_

However, it's never explained why next-generation whole genome sequencing will
lead to success for one endeavor but not for the other. He only says that
today's DNA chips (which don't reveal the whole genome) have failed to uncover
the genetic basis for disease.

------
Chi019
___No, Lewontin's fallacy is the belief that if this is true for every trait,
the populations are indistinguishable._ __

Physics Prof Steve Hsu explains the Lewtontin fallacy here:

Further technical comment: you may have read the misleading statistic, spread
by the intellectually dishonest Lewontin, that 85% percent of all human
genetic variation occurs within groups and only 15% between groups. The
statistic is true, but what is often falsely claimed is that this breakup of
variances (larger within group than between group) prevents any meaningful
genetic classification of populations. This false conclusion neglects the
correlations in the genetic data that are revealed in a cluster analysis. See
here for a simple example which shows that there can be dramatic group
differences in phenotypes even if every version of every gene is found in two
groups -- as long as the frequency or probability distributions are distinct.
Sadly, understanding this point requires just enough mathematical ability that
it has eluded all but a small number of experts.) Update: see here for an
explanation in pictures of Lewontin's fallacy. I also edited the paragraph
above for clarity.

On the other hand, for most phenotypes (examples: height or IQ, which are both
fairly heritable, except in cases of extreme environmental deprivation), there
is significant overlap between different population distributions. That is,
Swedes might be taller than Vietnamese on average, but the range of heights
within each group is larger than the difference in the averages. Nevertheless,
at the tails of the distribution one would find very large discrepancies: for
example the percentage of the Swedish population that is over 2 meters tall
(6"7) might be 5 or 10 times as large as the percentage of the Vietnamese
population. If two groups differed by, say, 10 points in average IQ (2/3 of a
standard deviation), the respective distributions would overlap quite a bit
(more in-group than between-group variation), but the fraction of people with
IQ above some threshold (e.g., >140) would be radically different. It has been
claimed that 20% of all Americans with IQ > 140 are Jewish, even though Jews
comprise only 3% of the total population.

    
    
        ...The imbalance continues to increase for still higher IQ’s. New York City’s public-school system used to administer a pencil-and-paper IQ test to its entire school population. In 1954, a psychologist used those test results to identify all 28 children in the New York public-school system with measured IQ’s of 170 or higher. Of those 28, 24 were Jews.
    
    

There is no strong evidence yet for specific gene variants (alleles) that lead
to group differences (differences between clusters) in behavior or
intelligence, but progress on the genomic side of this question will be rapid
in coming years, as the price to sequence a genome is dropping at an
exponential rate.

What seems to be true (from preliminary studies) is that the gene variants
that were under strong selection (reached fixation) over the last 10k years
are different in different clusters. That is, the way that modern people in
each cluster differ, due to natural selection, from their own ancestors 10k
years ago is not the same in each cluster -- we have been, at least at the
genetic level, experiencing divergent evolution.

In fact, recent research suggests that 7% or more of all our genes are mutant
versions that replaced earlier variants through natural selection over the
last tens of thousands of years. There was little gene flow between
continental clusters ("races") during that period, so there is circumstantial
evidence for group differences beyond the already established ones
(superficial appearance, disease resistance).

[http://infoproc.blogspot.com/2008/01/no-scientific-basis-
for...](http://infoproc.blogspot.com/2008/01/no-scientific-basis-for-
race.html)

------
rms
The comments on Reddit tear this apart but I don't think it's that bad.
[http://www.reddit.com/r/worldnews/comments/abjrm/human_genet...](http://www.reddit.com/r/worldnews/comments/abjrm/human_geneticists_have_reached_a_private_crisis/)

The two main points: genomic data is not as medically useful as family
history. What will be discovered is going to do very weird things to political
correctness.

Steve Murphy has loudly been expounding about the family history meme for
years now. <http://thegenesherpa.blogspot.com/>

~~~
cwan
I found the article to be unnecessarily patronizing. The idea that the general
public can't handle the truth on any number of subjects is simple arrogance.
Wasn't it revealed that McCain and Obama shared common ancestry way back? How
is it possibly even shocking that yes, there is "mis-attributed paternity and
covert mating between classes, castes, regions and ethnicities"?

Take this, one of the final and most bizarre statements: "If the shift from
GWAS to sequencing studies finds evidence of such politically awkward and
morally perplexing facts, we can expect the usual range of ideological
reactions, including nationalistic retro-racism from conservatives and
outraged denial from blank-slate liberals."

I agree with you - it'll be a blow to political correctness, but I'm guessing
there won't be the "nationalistic retro-racism" the author seems to hype - at
least no more so than exists now. But even for political correctness, there
will always be those who will deny that differences exist in the face of
evidence (just as in the case of "nationalistic retro-racism") as the recent
gender studies skirmishes show.

~~~
mlinsey
It was Obama and Dick Cheney.

------
dahv
This article completely side stepped issues of how important everything else
is to our lives. We won't solve disease by genetic knowledge. What food we
eat, the happiness in our lives, our exercise...these are so important.
Genetic knowledge won't teach us how to be healthy, just and peaceful.

As for the differences between the races, as much as they might exist, I can't
believe how people can be blind to how culture is extremely influencial.

Take your so-called smarter race (e.g. asian), take them to a "dumber" place
like America, and in a few generations they'll be just as dumb.

And the asians aren't smarter. I live in China now, teaching English. Their
education system, and the Asian education system in general (i.e.
China/Japan/Korea) strongly develops certain skills. Mostly, these involve
analysis, logic, and memorization.

However, while this form of education is outstanding for producing people that
can do very well at coursework and following directions (as well as become
excellent engineers/doctors/research assistants/accountants), it is very poor
at producing people who can think for themselves and be creative thinkers. It
certainly does not develop critical thinking.

As for the African stereotype...have you looked at what's going on over there?
Damn if I could study or learn shit if I'm a starving refugee.

Oh, and I can't believe nobody's seen the film "Gattaca."

~~~
w00pla
> Damn if I could study or learn shit if I'm a starving refugee.

You know that most (90%+) Africans are not starving? Africa isn't filled by
starving refugees as CNN would like you to believe.

I think the most common comparison with Africans is in the USA.

> Oh, and I can't believe nobody's seen the film "Gattaca."

This is an excellent (and was my favorite) movie and I identify strongly with
the main character.

While the movie sends a powerful image, now matter how hard you try, you will
not change a person's general intelligence (which is innate).

~~~
tokenadult
_While the movie sends a powerful image, now matter how hard you try, you will
not change a person's general intelligence (which is innate)._

What is the evidence for this? Most human behavorial genetics researchers talk
about a "reaction surface" set for each individual by that individual's genes,
but I'm not aware of any researcher who claims to have a proof for an upper
limit in how much "general intelligence" (that would be IQ) can change in the
case of individuals or in the case of populations. In fact, the existing
OBSERVED degree of IQ increases all around the world

<http://en.wikipedia.org/wiki/Flynn_effect>

has been described by N. J. Mackintosh in these terms: "the data are
surprising, demolish some long-cherished beliefs, and raise a number of other
interesting issues along the way." (Mackintosh 1998, p. 104). You write, "no
matter how hard you try," but it's not clear anyone is trying very hard or
very systematically to raise anyone's general intellilgence, but it is
happening anyway.

I meet weekly with human behavioral genetics researchers

[http://www.psych.umn.edu/courses/fall09/mcguem/psy8935/defau...](http://www.psych.umn.edu/courses/fall09/mcguem/psy8935/default.htm)

and have learned from them that the whole field of human behavorial genetics
is becoming much more conservative and cautious in its claims about genetic
limits on human potential than it was ten years ago. That's what is said
explicitly by Tom Bouchard, one of the most cited researchers in the field.

REFERENCE

Mackintosh, N. J. (1998). IQ and Human Intelligence. Oxford: Oxford University
Press.

P.S. Other good, recent reading on this subject is

Neisser, Ulric (Ed.) (1998). The Rising Curve: Long-Term Gains in IQ and
Related Measures. Washington, DC: American Psychological Association.

Flynn, James R. (2009). What Is Intelligence: Beyond the Flynn Effect.
Cambridge: Cambridge University Press.

~~~
w00pla
> claims to have a proof for an upper limit in how much "general intelligence"
> (that would be IQ) can change in the case of individuals or in the case of
> populations. In fact, the existing OBSERVED degree of IQ increases all
> around the world

I did not mention the Intelligence Quotient (which is subject to boosting). I
mentioned the general intelligence factor (which is mostly innate). Using
google scholar you can find many interesting articles about the general
intelligence factor and its neurological basis.

Using google scholar with “general intelligence factor” I found this article
that is cited 417 (it just struck my eye since the citations is extremely high
for such a recent paper):

A Neural Basis for General Intelligence Science 21 July 2000: Vol. 289. no.
5478, pp. 457 - 460 DOI: 10.1126/science.289.5478.457

This one just struck my eye, but there are many more. In my opinion general
intelligence factor has become beyond doubt – the question is now what the
neurological basis for intelligence is.

I also think that we will not do this complex and interesting topic justice if
we discuss it here.

~~~
tokenadult
The cited article (thanks for the citation to that year 2000 article, which I
wouldn't call "recent" on this subject) doesn't address the point I asked you
about. There isn't any proof whatsoever that current human beings are fixed in
"general intelligence" as soon as their genome is fixed. Rather, there is
entire agreement among all researchers that each human being's neurological
characteristics are shaped both by genome and by experience--on this point no
informed person has any doubt.

 _I also think that we will not do this complex and interesting topic justice
if we discuss it here._

You are welcome to speak for yourself on that issue, of course. But on my
part, I have observed that there are some HN readers who do their homework on
genetic and environmental influences on human intelligence before expressing
opinions on those issues, and I have learned from some of those participants
and so could anyone else who cares to read their comments.

 _I did not mention the Intelligence Quotient (which is subject to boosting).
I mentioned the general intelligence factor (which is mostly innate)._

It is for you to show that there is any practical way to make this
distinction, because general intelligence is investigated in human subjects
with IQ tests as the main instrument. See any of Ian Deary's extensive
writings on this subject for how difficult it is to identify "general
intelligence" without looking at IQ.

~~~
w00pla
> The cited article (thanks for the citation to that year 2000 article, which
> I wouldn't call "recent" on this subject)

The two books you’ve cited are older than this. An article with such a high
citation count is usually an old seminal work (citations increase with the age
of an article). For an article to have such a high number of citations in only
8 years is somewhat unusual (even when it is a Science paper).

> You are welcome to speak for yourself on that issue, of course. But on my
> part, I have observed that there are some HN readers who do their homework
> on genetic and environmental influences on human intelligence before
> expressing opinions on those issues, and I have learned

Again, I have pointed you to a treasure trove of information.

> because general intelligence is investigated in human subjects with IQ tests
> as the main instrument.

Not really. Raven’s progressive matrices (RPM) are popular. Another method is
a barrage of different intelligence tests (the more the better).

------
nazgulnarsil
the points are moot in a meritocracy. the only reason this is an issue is
because entitlements are at stake.

~~~
cabalamat
No, the reason its an issue is that people's emotions are tied up in their
opinions of their own species. They _want_ to believe cetain things about
humans, and when science shows them that reality is different from their
beliefs, some people take it very badly and refuse to accept reality.

A good example of this is the "controversy" over evolution v. creationism;
there's no real controversy, of course, but some people just refuse to accept
the reality of evolution so they've created a whole ideology of evolution
denial to boost their flagging self esteem. (I suspect that at some deep
hidden level, evolution deniers do accept it).

~~~
nazgulnarsil
good point. I harp about ideology being an inappropriate ego boundary
extension all the time but failed to apply it in this case.

------
lionhearted
Edit: Wow, this turned out to be long. Also, this is fairly politically and
potentially "identity hot" and I didn't add in a lot of caveats and
disclaimers. If I may humbly request, could you read at least halfway through
the comment before voting, and please write in and let me know if it offends,
or with any concerns or suggestions? Also, my email is in my profile if I seem
off and you're lurking without an account or don't want to comment publicly. I
imagine people could read a lot into what I'm saying that I'm not saying, so
please feel very welcome to make yourself heard by me if you disagree or
dislike anything I've put down. Also, I didn't mention any of the downward
spiral thinking that knuckleheads could potentially get into - and yeah, I
agree that stuff is ugly and we need to be careful, and no, I'm not a
knucklehead. Anyway:

I can tell a lot about someone by asking them in private, when it's just me
and them, "So... what do you think of genetic differences between races?"
Almost everyone, in private, will agree that there's some - but some people
are really, really uncomfortable saying it. Some people, especially very
diplomatic people, hedge and qualify first. When I make it known that I'm not
particularly judgmental, that I've had friends and lovers of all colors and
from all over the place, but that I also have a healthy respect for science
and reality - well, the diplomatic people tend to open up a lot more.

Basically I'll put it like this - people of difference descendencies have been
observed to have different average heights, weights, body fat percentages,
average musculatures, bone densities. Different kinds of blood cells even - if
you look at sickle cell anemia, blood cells shaped a little differently than
normal make a person more resistant to malaria, but more prone to anemia.
Malaria of course, being orders of magnitude more deadly and dangerous than
anemia, which is a more long term unhealthiness thing. And sure enough, sickle
cells are more present as an adaptation in people descending from formerly
high malaria areas - <http://en.wikipedia.org/wiki/Sickle-
cell_disease#Genetics>

Moving on - there's clearly slight variances and differences between people of
different descendants. The idea that there's no cognitive differences just
seems incredibly unlikely. Now, I think "IQ" or "intelligence" is drastically
oversimplified and bunk. But things like abstract recall - how fast can you
remember something? Pattern recognition. Dexterity and coordination. And so on
- why _wouldn't_ these things be adaptable and heritable? Wouldn't some parts
of the world being able to remember a skill after not using it for a long
period of time be more valuable than others? (places with harsh winters, for
instance?) The ability to think quickly and adapt be better in different
places? And if they were, wouldn't you expect natural and sexual selection to
make the local population more like that?

This is almost all moot in many practical ways - the only thing that bothers
me is that since people don't want to acknowledge that these differences
exist, there's been very little work to learn teaching styles that would apply
to different people, how different medicine and diet regimes would work
better, and so on.

Different groups of people tend towards different lactose intolerance and
alcohol intolerance levels - this is only recently being considered in
nutrition and diet because the implications of it - different food good better
for different races - is not a good political position these days. It would
have been easy to test for lactose sensitivity among different groups of
people and make recommendations 20-50 years ago, but no one wanted to touch
it. Instead, "milk for everyone!" was the official position, which is
nonsense. Dairy is terrible for the people it's bad for.

Finally - I'm very curious about what the effects of mixing blood in children
would be, and there's been very little research that I know of. From my
understanding of genetics, mixed blood children should be particularly strong.
My background is mixed Western/Eastern European, and I'd prefer a wife of
different bloodlines than my own, as I think it's a very positive thing to do
for my children. Obviously you can't control who you fall in love and connect
with completely, but if I choose to live in Ankara or Osaka instead of London,
that greatly increases the chance my kids are half-Turkish or half-Japanese. I
think that'd make them stronger, healthier, and less prone to some of the
negative things in my bloodlines. But how much so? When parents have different
cognitive backgrounds, which are dominant? For instance, if one parent has
much higher natural testosterone levels, is that dominant? That means the
children would have higher energy, be more resistant to some diseases, be more
willing to act independently and defy consensus, but also have more proneness
to violence, anger, and aggression. I generally have high testosterone
throughout my family - we've made good soldiers but some of us have had pretty
bad tempers. What happens if I marry a woman with a lower natural
predisposition towards testosterone? How about different cognitive abilities?
We've generally got bad eyesight and bad spatial relations in my family. You'd
expect good eyesight should be a dominant characteristic, no? But how much so?

I'd love to see research on this, and I think we will, because you can only
hold back science and knowledge through moral fashion for so long before it
breaks through.

~~~
CamperBob
_The idea that there's no cognitive differences just seems incredibly
unlikely._

As long as the difference between individuals in a single population is
greater than the mean difference between populations themselves, I don't see
much relevance.

Sure, Negroid races as a group don't have the IQ of Caucasians. But Caucasians
who attach any importance to that had better look over their shoulder at the
Asians, who in turn beat _them_ on the same tests. The Asians don't want to
get too smug in a room full of Ashkenazi Jews. Meanwhile, there are plenty of
individual Negroids and whitey-birds who outperform plenty of individual
Asians and Ashkenazis.

If any lessons have emerged so far from the study of human genetics, it's that
your genes are not your destiny. In any just society, an individual's success
will always consist of 90% perspiration, 8% inspiration, and 2% DNA.

~~~
w00pla
> As long as the difference between individuals in a single population is
> greater than the mean difference between populations themselves, I don't see
> much relevance.

This part is the Lewontin's fallacy
(<http://en.wikipedia.org/wiki/Lewontin%27s_Fallacy>)

~~~
yummyfajitas
No, Lewontin's fallacy is the belief that if this is true for every trait, the
populations are indistinguishable.

------
gfodor
Shooting down the notion that genetics are tied to race and thusly tied to
positive or negative traits brings really brings out the anecdotal evidence
logical fallacy in full force.

Just remember, anecdotal evidence is largely the same "logic" used by racists
to justify broad stereotypes of people.

------
kingkongreveng_
> the genes typically do not replicate across studies. Even when they do
> replicate, they never explain more than a tiny fraction of any interesting
> trait.

Epigenetics. Diet and lifestyle have large effects on how a genome is
expressed. And even on how the genome is expressed in future generations.

I thought this was well understood? Why no mention of it in the article?

------
cryofan
oh, no, if genetics reveal differences in humans, then that will make it
harder for the rich people to combine many races into each workplace, each
neighborhood, each city and each nation. Diversity is how the rich people
divide the population, and if the population cannot be divided, then the
population will unite against the rich.

Remember, Kids--Diversity is strength....(for the rich)

