
Association between polygenic risk scores for ADHD and cognitive outcomes - gwern
http://ije.oxfordjournals.org/content/early/2016/09/28/ije.dyw216.full
======
axoltl
I'm always curious when research like this comes out, as it flies in the face
of my (admittedly anecdotal) evidence. I myself am diagnosed with ADHD-PI
(Primarily Inattentive). I've also been part of a few hacker groups over the
years, and they had/have the best and brightest minds I have ever witnessed.
They have an uncanny intuition and ability to traverse complex problem spaces,
much faster than most people. There is also an unusually high concentration of
people with ADHD in these groups (along with some other mental 'inflictions').
My best guess is anywhere from 20-30% of them have ADHD to some degree, sample
size is about 30.

Most of these people do fairly well in life. Their skills are extremely
valuable and prized. They also almost always (95-99%) did not do very well in
school. There are a couple of explanations:

1\. Studies like these simply track educational achievements, which do not
necessarily correlate with success in life.

2\. I only ever see/meet the success stories, each of which there is a much
larger amount of failures for.

3\. There are multiple conditions that are all erroneously grouped under the
moniker of ADHD. Most, if not all, of the successful ADHD people I know lean
more towards the inattentive side of things.

4\. Some combination of the above theories.

~~~
slezakattack
I think for every batch of successful people with ADHD, there are others still
finding their way. I have ADD and my brother has ADHD. I'm super quiet,
observant, and methodical at times. He's very energetic, passionate, "never
give up" kind of personality. It's interesting to see the similarities and
differences between us. I'm not sure if it's related to the mental disorder or
just hereditary or shared personalities from growing up together, but we both
didn't do well in school as our parents would hope. He was definitely a
troublemaker and I was just..in my own world I suppose. I'd like to think I'm
"successful". I have a steady job and able to pay the bills while affording
the thrills of life. I'm extremely grateful. My brother, on the other hand,
lives with my parents, working 60 hours a week and has no health benefits or
paid time off. Perhaps it's part of "growing up" and I just got lucky. I'd
like to think that him and I look at the world from a different lens from
others but I don't think it's affording us any sort of life hacks that make us
successful or brilliant.

~~~
angry-hacker
I agree. It's just like the myth of gay people (usually being told by
conservatives) running the world and being the wealthiest, because watch these
famous gay people and Tim Cook. Ignoring the population as whole, many in very
bad situations.

------
jbrambleDC
I was once diagnosed with ADHD myself as a child. I have been unmedicated for
8 years now and been quite successful career wise, and academically. Though I
do wonder if I could do better had I not had ADHD.

its not fair to conduct these studies solely on educational outcomes because
educational outcomes in the west largely depend on how well you conform to the
mean societal expectation of a successful archetype. many people have unique
educational styles (ADHDers included). I myself personally learned more from
the internet and reading books than I ever did in school.

I suspect successful engineers, start up CEOs, hacker types have higher
prevalences of "learning disorders", ADHD, etc. Many did poorly in school,
though many also excelled. I also suspect the same demographics are true of
musicians and other artists.

The MAJOR caveat here, is that while these groups probably have higher
prevalences, and these fields are more or less supportive of people with these
issues, very few ADHDers can break into these fields and the average ADHDer
probably will perform worse in life than the average person without.

Mostly conjecture, based on my own anecdotal evidence, but worth
consideration.

------
safanycom
Dodgy data.

In the UK/IE system GCSEs morphed between 1990 and 2010 with exams replaced by
coursework - which is quicksand for ADHD types. This is a coursework cohort
from 2007-2008.

Now and before 1990, GCSEs at 16yo are memory tests in an exam hall almost
designed for hyperfocus. It is relatively easier for a ADHDer to "wing it".

What would be more interesting, is to see how many fell down on mainly course-
work assessment versus mainly exam assessment. Also, comparison between 16yo
GCSE results and 18yo A level results.

[Disclaimer: ADHD PhD who failed A Levels]

------
dweekly
Can someone summarize this for me? ;)

------
marcoeur5
Hi. I'm 10. I have ADHD and ODD. I'm smart but frustrate easily and call
people stupid. But If I can escape the anxiety I am nice. Advice?

~~~
keenmaster
Assuming you're not trolling, it's impressive that you're 10 and on HN. I
think modern culture, in a bad way, encourages people to take their
inclinations to the extreme. If you have ADHD, you're not just someone with
that particular medical condition, you're "an impatient genius who has no
tolerance for BS or stupidity." That's not to say you think of yourself as
such, just that people are rewarded for acting consistently with a memefied
Hollywood stereotype of themselves. This in turn influences and reinforces
behavior.

Focus on how you can utilize your mental makeup to shape your life rather than
bend others. Reduction of zero-sum dog eat dog thinking would help ameliorate
any social aspect of your anxiety. I didn't have much to go off of from your
post but I hope that helps.

~~~
mrkgnao
I'd say it's not so much as _impressive_ as it is _fortunate_ ( _providential_
, even) for someone with a certain kind of mind: I would definitely have
benefited if I'd found HN a few years earlier than I did (rather than Reddit,
ha).

------
AlexCoventry
Has GWAS become a reliable means of identifying causal variants? How have the
methods evolved over the last five years? What are the big success stories?

~~~
a_bonobo
I work a bit in the field - GWAS is still not identifying causal variants,
only linked variants.

There are tons and tons and tons of publications that keep on getting
published on running similar datasets with the same methods (PCA, regression
or MLM, done) and then reporting the associated SNPs. In humans these papers
are getting huge with massive datasets, like this one:
[http://biorxiv.org/content/early/2015/05/27/019885](http://biorxiv.org/content/early/2015/05/27/019885)

There was also this interesting paper which relied on a very specific
configuration of a human population, you cannot do that with for example
Brits:
[http://biorxiv.org/content/early/2015/11/12/031518](http://biorxiv.org/content/early/2015/11/12/031518)

By its very nature GWAS cannot prove a causal relationship, I'm now hoping
that CRISPR-Cas9 can provide for that - use GWAS to find candidate SNPs, use
CRISPR to introduce those SNPs in an unaffected population, measure phenotype
changes. Of course with sequencing getting so cheap you can start with SNP
calling and get a much more comprehensive picture by looking at large scale
insertions and deletions by just looking at the whole genome, like this paper
for 10,000 (!!!) humans:
[http://biorxiv.org/content/early/2016/07/01/061663](http://biorxiv.org/content/early/2016/07/01/061663)

~~~
AlexCoventry
Thanks. Are the GWAS's the primary justification for the sequencing efforts
generating the data they're analyzing?

~~~
a_bonobo
I'd say the primary motivation for the sequencing efforts is that we're
hitting the limits at what we can detect using SNPs. We now know of many
inversions, deletions, insertions which are linked to phenotypes, and often
you don't have a SNP positioned close enough to detect a signal. It's just
easier and more comprehensive to align the genomic reads directly to detect
these rearrangements than it is to look for a null signal in the SNP dataset.

~~~
AlexCoventry
What do you do with those associations, once you've found them? Are they
helping to elucidate the biology of the phenotype?

~~~
a_bonobo
There are many things you can do with the association, here's a non-exhaustive
list:

\- do the SNPs cause changes in a gene of interest? are the changes synonymous
(cause base change, but the protein amino acid is identical since several
codons code for the same amino acid, but this can cause problems in mRNA
folding)? Are the changes non-synonymous (cause base change, and a different
amino acid)? How strong are the non-synonymous changes? It could be that you
get a shorter protein because a SNP introduced an early STOP codon, or changes
a hydrophile to a hydrophobe amino acid, etc. From there you can check whether
this change influences the phenotype by introducing this changed protein into
another individual to see whether the phenotype is reproduced, this rarely
works in more complex species as you don't have a single gene -> single
phenotype cause

\- you can use the ratio of synonymous/non-synonymous SNPs to approximate
selection: genes under positive selection show more non-synonymous changes,
these are usually genes involved in resistance who have to keep up with
fungal/viral invaders, or venom genes, etc., genes under negative selection
show more synonymous changes, these are usually housekeeping genes or other
single copy genes that are important

\- are the SNPs closely upstream or downstream from a gene of interest? It's
still a bit hard to find binding sites for transcription factors (esp. outside
of model species), so the SNP could be in a binding site where the whole
transcription apparatus binds - do we see different transcription level for
this gene in other individuals without the SNP?

\- after DNA folding, is the SNP close to an interesting gene? Only with new
HiC data can we test this, SNPs that were >10,000 base pairs away are after
folding right next to the gene

\- is the SNP in Linkage Disequilibrium with something interesting? In other
words, is the SNP inherited together with something interesting? This could
point towards selection

------
blakesterz
_Conclusions: ADHD diagnosis risk alleles impact on functional outcomes in two
generations (mother and child) and likely have intergenerational environmental
effects._

So, ADHD is frequently heredity based on certain genes?

Why oh why oh whyyyyyyyy must academics write like this still?? (I know the
answer, doesn't stop me from complaining)

~~~
Itaxpica
Because that's not what that sentence means.

Jargon in academia is definitely overused, but in this case the terminology
they're using has specific meanings, that this is meant to communicate to
people within the field, that are lost or obscured when you attempt to
simplify them.

~~~
spangry
So what does it mean? If GP's interpretation is incorrect then I'm also
baffled. And I'd really like to know because I have ADHD...

~~~
fleitz
They found a correlation between ADHD and low IQ/test scores.

I had shitty marks in HS too, didn't go to college and am highly successful

~~~
stagbeetle
As someone with ADHD who had shitty marks in HS, is probably going to drop out
of college, and wants to be successful -- can you give any insight on how you
got where you are?

~~~
fleitz
Brush up on your social skills, hacking computers are nowhere near as valuable
as hacking people.

Be CEO of something, dress sharp, get fit. How you look, act, and dress is
your UI most hackers have a really shitty UI. Get a good logo, great cards and
a good website / brochures. Pay others to make these things, use fivver, put
everything out to bid, some people are really cheap, don't be afraid to hire
people undercharging for their services. Tip them so you get prioritized.

Sell something repeatable, anything you can pay someone else to do, pay them.
Get a lawyer, a good accountant, create your own contracts, run any serious
changes by them.

Make sure you have quotes from your subcontractors, double it. Triple it. 10x
it. Charge that to your clients. The more you charge the better you are.

Basically be the fucking man. Don't apologize for it.

Read everything by Robert Cialdini. It's a hacking guide to the masses. Read
how to win friends and influence people it's a guide to hacking individuals.

Realize everyone is winging it and actors are doctors when they wear lab
coats, lawyers when they wear suits and bikers when they wear leather. It's
not hard to pass for anything wearing the right clothes.

Don't be afraid to bill $500 for something you paid $24 for. Never tell people
how much something cost you or where you sourced it from.

Be really nice and highly complimentary to people.

~~~
stagbeetle
Appreciated.

I had passed off Cialdini's books for dirty salesman tactics, but I'll get to
it now.

~~~
fleitz
Thinking of successful people as dirty is the first thing to get out of your
head. Don't be a hater. I did for years it got me nowhere.

A pretty much universally reviled dirty salesman is the President of the
United States and most of the people who hate him are not.

Cialdini was also Obamas Comms guy so people you might like also use him.

The question is do you want to not use cialdinis tactics or do you want to be
President, both are honorable choices.

Many people who don't want to use his tactics will be your employees.

Also read / listen to Thomas Sowells basic economics and understand the short
and long term debt cycle.

~~~
stagbeetle
I understand.

I've picked up all the books you recommended and I'll get through them
tomorrow.

Is business at that level all about working people?

~~~
fleitz
Yes and no, it's about understanding their needs and providing a solution
while also charging enough to pay for everything and future expansion. Also at
the same time you need to cut costs to deliver efficient solutions in the
future.

If you price everything based on living in a dorm, underpaying yourself, etc
your business would fail.

If I didn't charge $500 for something with $24 in direct costs I wouldn't have
time to meet with clients, go to networking events, pay for my time for all
these things, pay for insurance, pay for nice clothes, pay my trainer, etc,
etc, etc.

Initially it's best to think of things as massively over charging because it's
way too complicated to actually figure out what things are really costing you.
Plan for future expansion, etc.

But yes at a higher level people are going to try to get you to undercut
yourself, if you give into the idea that you are over charging you'll end up
being taken advantage of. So initially you need to be very strong in your
boundaries until you have full time staff to do a proper analysis.

If you roll up in a Mercedes and a nice suit people take you much more
seriously than in a beat up Toyota and some rags, you'll also project more
confidence, people are buying you, not your product.

Also with all this stuff learn body language, slow down how fast you talk,
slow down how you walk, do everything as if it's just a sure thing that's
going to happen

~~~
stagbeetle
I'll implement this advice.

I've picked up _The Silent Language of Leaders_ and _What Every Body is
Saying_ for body language, and another for persuasion: _The Like Switch._

Would you recommend learning how to shake hands/assert dominance like Trump,
or is that something that might start being fazed out?

Also, when you get "fuck you money," will toning down on the theatrics hurt
you in a major way, even if you've already shown you can be a BSD and preform?

~~~
fleitz
Dominance isn't being phased out, it goes back to the great apes.

I dunno, I think if anything fuck you money will make me up the antics

