
Forecasts of genetic fate just got a lot more accurate - rbanffy
https://www.technologyreview.com/s/610251/forecasts-of-genetic-fate-just-got-a-lot-more-accurate/?utm_source=twitter.com&utm_medium=social&utm_content=2018-02-28&utm_campaign=Technology+Review
======
a_bonobo
>Such predictions, at first hit-or-miss, are becoming more accurate. One test
described last year can guess a person’s height to within four centimeters, on
the basis of 20,000 distinct DNA letters in a genome.

I find that comparison highly misleading, height was always a reasonably
'simple' trait with very high heritability that is (in our society) relatively
uninfluenced by environment. Here's a 2009 paper showing that you can predict
height reasonably by averaging the parents' height (the 'Victorian method').
[https://www.nature.com/articles/ejhg20095](https://www.nature.com/articles/ejhg20095)

It's one of the few traits where you can do that well, so why would you use
that as an example as to why genetics-based tests are getting better? All
other phenotypes/traits are much more complex.

>When they built a predictor for coronary heart disease, for instance,
Kathiresan’s team discovered that the people it predicted to have the very
highest risk, the top 2.5 percent, had four times the average chance of
developing clogged arteries.

So what's the base risk? If the base risk is 0.0005% then a four times higher
chance is still tiny.

I think it's this paper:
[https://www.nature.com/articles/ng.3914](https://www.nature.com/articles/ng.3914)
As the scientists correctly pointed out, they only looked at Europeans, so who
knows how this fares with Asians or Africans (likely: not well). None of the
odds ratios are above 1.1, most are around 1.05, not a very extreme change to
me!

Why this matters: In countries like Australia, unlike Germany, there is no
protection by the law from insurance companies who don't understand genetics.
People can and have lost life insurances due to the results and questionable
interpretations of genetic tests. I can only hope politicians don't read this
article.

~~~
gwern
There's nothing misleading about it, nor does height have a uniquely high
heritability You can also predict childrens' adult IQ and many many other
traits to similar degrees based on mid-parent regression, because they are all
genetically influenced.

The point of the height GWAS example is that because it is so very obviously,
even to the naked eye of the layman, genetically influenced and objective (you
can't argue height doesn't exist), it serves as a simple test. If GWASes can't
predict height, they probably can't predict anything else. And this was
exactly how height was used back in 2009 or so when the 'missing heritability'
debate was still going: if all these traits are genetic and additive, why
aren't the GWASes able to find anything for height (back then)? The answer
turns out to simply be that there wasn't enough data and the linear model
analyses were lousy. Now there is enough data and better algorithms are being
applied, so as expected, height prediction works much much better.

> All other phenotypes/traits are much more complex.

No, not really. That sort of polygenicity is the norm. Look at, for example,
Shi et al 2016 which attempts to model the distribution of effects & thus
polygenicity of 30 human complex traits:
[https://www.biorxiv.org/content/early/2016/01/14/035907](https://www.biorxiv.org/content/early/2016/01/14/035907)
. Height doesn't exactly pop out of any of the charts.

> So what's the base risk? If the base risk is 0.0005% then a four times
> higher chance is still tiny.

...coronary artery disease should be quite obviously a higher base rate than
0.0005%. In any case, I believe the referenced study is Inouye et al 2018, in
which case the extremized prediction is ~8% vs ~30% lifetime risk:
[https://www.gwern.net/images/genetics/2018-inouye-cad-
riskpr...](https://www.gwern.net/images/genetics/2018-inouye-cad-
riskprediction.png)

> None of the odds ratios are above 1.1, most are around 1.05, not a very
> extreme change to me!

It's the total that matters.

~~~
gwern
(Or look at Zhang et al 2017 comparing complex architectures:
[http://www.biorxiv.org/content/early/2017/08/11/175406](http://www.biorxiv.org/content/early/2017/08/11/175406)
)

------
tinokid
C'mon people...this is not science, this is fortune telling. They are just
doing a bunch of huge multiparameter curve fits, which are going to pick up
signal from all sorts of things that have nothing to do with biology no matter
how big their sample size is. These people will tell you with a straight face
that a bunch of markers that just happen to be associated with "Northeast
European ancestry" are also predictive of "Polka dancing ability," and their
papers are shuffling and repackaging thousands upon thousands of nonsensical
little tidbits exactly like that. Life experience doesn't just "average out."
Do better.

~~~
ggggtez
Do you believe statistics aren't real math? I'm not sure why the complaint.
Sure it may be inaccurate, but as others said, along questions like: "do you
have X heritage?" are _already_ used as predictors for certain diseases.
Genetic investigations just gets a little closer to the base truth, even if no
one knows exactly which genes are doing which things.

~~~
Balgair
I think GP is talking about Type I errors; where you go hunting for
correlations that are p<0.05 in a data set.

[https://en.wikipedia.org/wiki/Type_I_and_type_II_errors](https://en.wikipedia.org/wiki/Type_I_and_type_II_errors)

------
Gatsky
So if I have a higher risk of heart disease than average, the advice will be
to eat well and exercise. This is indistinguishable from the current
guidelines without any genetic information.

No rational human being should consent to their genetic information being
correlated with their IQ. This kind of data is a surefire way to convince
otherwise entirely capable people that they should give up on life. It's
abhorrent that anyone could conceive of trying to make money out of such a
test.

~~~
prepend
Adhering to that basic advice is hard. Most people don’t do it. I’d like to
see a study if adherence to diet and exercise improves with genetic
predictions.

For me, it would help to have a somewhat accurate prediction tied to my Fitbit
that shows me right now the benefit of my hour cardio every day. My doctor
could look at my physical activity vital signs pulled from wearables during my
physical and give me personalized advice “You’re going to die 6 years earlier
because of your genes+your diet+your excercise with 20% margin.” Is a lot more
effective than “your diet and excercise suck, it will have some unquantified
negative impact. But you might be fine, who knows.”

~~~
Ultimatt
You might want to sign up to be interested in our upcoming consumer product
then ;D
[https://www.genetrainer.com/signup/](https://www.genetrainer.com/signup/)

But the idea that you have absolute risk/gains from just genetics is a little
unreasonable in the world of health rather than disease. For example you might
have a predisposition for being incredibly stubborn and single minded (a
mental trait) and utterly overcome any slightly weak cards nature dealt you
for your physique. I think almost everyone can relate to that concept. We all
put effort into our weaknesses most of the time, and then become highly
proficient almost in what we are worst at innately! If you were told somehow
your IQ is genetically average... so? IQ is a sliding scale constantly
normalised as time goes on. Average IQ now is relatively much higher than a
hundred years ago. The same is true with sporting achievement we have seen
linear improvement in almost every sport since records started. At some point
we will reach the limitation of sports science and brush up against genetic
hard realities about physical muscle or oxygen transport. But not yet, and not
for most people wishing to become fit and healthy. It's a genuine mix of
genetics and what you are doing with your life, not some block thats genetic
and then lifestyle both influence each other. You can live your life slightly
abnormally to maximise your genetics. That function is very complex and
personal. To talk of average risk change with genetics is almost to completely
go against the whole point of the technology!

~~~
prepend
Thanks. I signed up for your beta and when check it out when I get an email
seems interesting.

While I agree that genes aren’t absolute, but 1) sometimes it’s pretty close
and 2) it doesn’t need to be absolute if it results in improved rates of
behavior change.

I’m familiar with a condition with really high penetrance. So while not
absolute it’s really high and almost a certainty. If computing could tell me
how different risk factors or behaviors could offset or mitigate in
understandable terms, that would be useful.

I’ve looked at sites and they all seem to reflect pretty blah guidance that
isn’t specific enough to be able to model personalized changes. But I expect
that to change with all of these large genetic data sets and trials going on.

Being fit and healthy would be great for everyone. But 60% of the US isn’t
oversight or obese because they are stupid or lazy. It’s just hard and made
harder by a very disconnected feedback loop.

------
matte_black
I love stuff like this. What we need now is a service that can estimate
potential genetic outcomes when having children with a partner. This can
finally open the door to making genetic information a standard in dating
profiles.

Instead of choosing partners based on short term metrics and hoping for the
best, people would be able to select with more confidence that their children
with someone would come out the way they like.

To me this kind of tech is a great way to leave a dent in our universe. A
world filled with smarter, stronger, and calmer children is a world that is
eventually filled with smarter, stronger, and calmer adults, who then go on to
have even better offspring and accelerate the evolution of mankind into a more
civilized species. Perhaps then we can finally see the end of war and
ridiculous squabbles over matter.

I personally may take a stab at creating a dating service like this if the
pieces are all there someday, but I’d hope by then someone else will have
beaten me to it.

~~~
ilamont
_people would be able to select with more confidence that their children with
someone would come out the way they like._

In other words, a eugenics profile.

Why stop at dating apps? You could put the data mortgage applications,
insurance profiles, and more. I can imagine some of the conversations wouldn't
be too far off this:

"I love you, but with a 22% chance of our kids having brown eyes and a 56%
chance of high cholesterol, I have to end the relationship."

"The bank denied the application, because you're at a higher risk for a
myocardial infarction by the age of 50."

"My car insurance rates will go through the roof if I put you on my policy
because you're genetically predisposed to drive more aggressively than me."

~~~
cm2187
But doesn't that eugenics happen naturally already? Like people of similar
race, centers of interest, character or intelligence having a higher
likelihood to form a couple and if DNA has anything to do with these
characters, re-enforce these traits in their children? All that will change is
that people will be aware of it.

~~~
faitswulff
No, not really. Eugenics includes ideas like forced sterilization of
"undesirables." I doubt you're advocating for that.

You could argue that the opposite of what you describe is happening. health
tech means that many selective forces like congenital diseases and birth
defects have less of an effect. Online dating also seems to have increased
interracial dating.

What _is_ happening and has scary ramifications for society is called
assortative mating, which normally happens along educational and financial
lines: [https://www.economist.com/news/united-states/21595972-how-
se...](https://www.economist.com/news/united-states/21595972-how-sexual-
equality-increases-gap-between-rich-and-poor-households-sex-brains-and)

~~~
colmvp
> Online dating also seems to have increased interracial dating.

Anecdotal but as an Asian male this hasn’t been the case for me at all. I
posted my stats on HN a few months ago but from thousands of profile
interactions I’ve had practically zero mutual interest from non-Asians. That’s
not an exaggeration either, I literally have a zero percent approval rate from
white women, the majority ethnicity in my current city.

Every single Asian male friend that I know of didn’t meet their non-Asian SO
online dating, but met them in person from work/school/group events. Likewise,
every non-Asian female I’ve ever dated I met offline first.

~~~
faitswulff
Since I'm also a straight Asian male, I can empathize:
[https://www.npr.org/2018/01/09/575352051/least-desirable-
how...](https://www.npr.org/2018/01/09/575352051/least-desirable-how-racial-
discrimination-plays-out-in-online-dating)

When I was dating, it seemed like anyone interested in me was either an otaku
or a weeaboo :p

However, the data regarding interracial dating says otherwise:
[https://www.technologyreview.com/s/609091/first-evidence-
tha...](https://www.technologyreview.com/s/609091/first-evidence-that-online-
dating-is-changing-the-nature-of-society/)

Note that the future may not have arrived in all places equally at the same
time.

~~~
cm2187
But a rise in inter-racial dating (from very low levels) is not incompatible
with same-race dating still being dominant.

------
agentgt
I’m just not comfortable with this. Maybe I’m just getting old and maybe I
have seen too many movies but I feel uneasy about our children and maybe us
having another “grade” put on them.

I’d like to think this would be good so maybe some one will comment how this
won’t eventually go too far.

If altering starts happening which I would imagine it will at one point will
be no longer human (and maybe that is a good thing).

Maybe at some point like in the Altered Carbon series it won’t even matter and
it will just go back to money (or maybe it will always be the case as the
ultimate grade).

~~~
cm2187
But these studies are merely going to give you a correlation. It will always
be very hard to prove direct causality without experimentation, which on
humans is not really feasible or without a full understanding of how the brain
works, which we are still very far from.

The other thing is that the way I like to think of our brain is like a muscle.
Our DNA drives much of the range in which we can develop our muscles, people
born with a certain body type will never be an athlete, but even if you are
born with good muscular capacity, a KFC-eating couch potato will never get to
the olympics. What one does with this capacity matters a lot. Only science
will tell but I like to think that the brains works in a similar way. Some
kids will never be geniuses but there is still a wide range in which they can
evolve so there is no reason to corner them in a box.

~~~
maxerickson
Even trained practitioners have trouble treating statistics like statistics.
For example, the anecdotes in
[http://www.bbc.com/news/magazine-28166019](http://www.bbc.com/news/magazine-28166019)

So the idea that people in general aren't going to mistreat and over-interpret
the information gathered is a little ambitious.

------
nukeop
Here's my wild prediction for the 21st century: before 2050, China will
replace its one child policy with a "you have to be at least this tall to
ride" policy - only people with a genetic "score" of X or higher are allowed
to reproduce. Every couple of years, X is bumped up, and the next generation
is a bit smarter, prettier, and stronger than the previous one.

~~~
cybertronic
An ever smarter/stronger population could be a threat to China leadership.

~~~
yorwba
Not if they are also bred to be more conflict-averse. Additionally, the
leadership would probably get preferential access to genetic treatments and
favorable mating partners.

------
philipps
This is exciting and worrying in equal parts - can’t wait for the Black Mirror
episode.

~~~
beckler
Why wait?

[https://en.m.wikipedia.org/wiki/Gattaca](https://en.m.wikipedia.org/wiki/Gattaca)

------
BatFastard
Great techno adventure book on this subject by [http://daniel-
suarez.com/](http://daniel-suarez.com/) "Change Agent" This guy has more
insightful ideas in his first 20 pages than most authors have their whole
lives.

------
gaius
Combine this with a private insurance based healthcare system and you’ve got
the perfect storm.

~~~
tanilama
Depends on how accessible this is.

------
wiz21c
Does anybody know how specific/sensitive those polygenic tests could be ?

Answering my own question :
[https://en.wikipedia.org/wiki/Polygenic_score](https://en.wikipedia.org/wiki/Polygenic_score)

------
JoeAltmaier
I can predict things like height, too. And I don't need your DNA. You're 5'9".
I'm right, within 4 inches, because 80% of everybody is within 4" of 5'9".

------
cm2187
Using DNA to predict the likelihood of a behavior or IQ is on a collision
course with the ghost in the machine doctrine, which assumes our intelligence,
character, what we become is solely or predominantly the result of our
environment/culture/education. I wonder how far research in that field can go
before it is decided that the potential outcome would be politically
unacceptable.

~~~
quotemstr
Modern-day lysenkoism disappoints me. The blank slate model is thoroughly
discredited, and people as eminent as Pinker have written extensively about
it. While you can still find plenty of blank slate support in polite society,
those espousing the idea are operating under something akin to religious
faith.

~~~
crowbahr
I'm genuinely curious: where can I read the disproving of tabula rasa?

Are you meaning moral blank slate, intellectual blank slate or some
combination of them?

