[HN Gopher] Integrating variants in 42k autism cases identifies ...
       ___________________________________________________________________
        
       Integrating variants in 42k autism cases identifies mutations in
       new genes
        
       Author : bookofjoe
       Score  : 53 points
       Date   : 2022-08-19 12:32 UTC (10 hours ago)
        
 (HTM) web link (www.nature.com)
 (TXT) w3m dump (www.nature.com)
        
       | swayvil wrote:
       | People "on the spectrum" make the best
       | engineers/scientists/artists. They are really good at
       | concentrating.
       | 
       | Maybe a little autism is good for our society. Maybe we don't
       | want to cure it so much as temper its more extreme cases.
        
         | alistairSH wrote:
         | That's a vast over-simplification and over-generalization of
         | ASD. And completely ignores the negatives associated with these
         | mutations.
        
           | swayvil wrote:
           | I addressed that a whole 1 paragraph down.
           | 
           | Sometimes I think that refutation is inherently more
           | attractive than discussion or support. What you think?
        
             | feet wrote:
             | Not really, and the replier's point still stands. ASD has a
             | wide range of phenotypes and not even close to all of them
             | are "good at concentrating"
        
             | alistairSH wrote:
             | Sorry, you made such a sweeping and incorrect
             | generalization that I didn't think a detailed response was
             | warranted. But, since you asked...
             | 
             | "really good at concentrating" by itself is not autism. And
             | as a trait, it is far from universal among people who have
             | ASD. And for those with ASD who can concentrate, that is
             | sometimes to the point of being a disability (hyper-focus
             | to the point of ignoring all else, including personal
             | care). And there's really no such thing as "a little
             | autism" - it's a spectrum defined by having some
             | combination of a larger set of deficits.
             | 
             | If I come across a little snippy, it's because I raised a
             | child on the spectrum. He's now a successful, independent
             | adult, but it wasn't an easy process for him or the rest of
             | the family.
        
         | matheusmoreira wrote:
         | On the contrary, cognitive impairment is common in autism.
         | You're probably thinking of attention deficit disorder which
         | paradoxically may present with hyperattention, usually when
         | something is very interesting to the patient.
        
           | swayvil wrote:
           | I used the term "the spectrum". It covers everything from
           | casual obsessives to serious handwavers
        
             | emrvb wrote:
             | Which is another indication you are not very knowledgeable
             | on the subject. ADD/ADHD are disorders on their own. It is
             | a common comorbidity for people on the spectrum, but it's
             | certainly not part of the spectrum.
        
             | galgalesh wrote:
             | Just a technical note: "spectrum" in autism spectrum
             | disorder doesn't refer to a scale from "mild" to "strong",
             | but refers to a spectrum of symptoms/behaviors.
             | 
             | There is a broad spectrum of symptoms which fall under the
             | autism spectrum. Everyone who has ASD, has a number of
             | these symptoms but two people who both have ASD can easily
             | have none of these symptoms in common.
        
         | pingeroo wrote:
         | Some aspies are awesome others are asshats -- like anyone else.
         | Am somewhat envious of the Vitalik types but at the same time I
         | wouldn't trade my "neurotypical" brain for an autistic one.
         | 
         | I am a social animal. I like getting along with people. I like
         | being able to feel how others feel by hearing their tone of
         | voice or looking at their face.
         | 
         | If I wanna concentrate I consume caffeine.
        
           | Melting_Harps wrote:
           | > . Am somewhat envious of the Vitalik types but at the same
           | time I wouldn't trade my "neurotypical" brain for an autistic
           | one.
           | 
           | I'm genuinely curious, you'd want to be a person who
           | developed perhaps one of the most needlessly complex and
           | obtuse programing languages riddled with bugs and have an
           | even more nebulous idea of what it's built for but assured
           | everyone it was to revolutionize the World via something VC
           | scammers would eventually call Web3 after failing to build
           | the first 'global computer'?
           | 
           | To date, Vitalik represents exactly what HN seems to think
           | about crypto; lots of promises with no real use-cases which
           | all end up as vapourware and exit scams.
           | 
           | I've been in this since he was in an Unsystem member
           | squatting with Amir, and to be honest the only way I can
           | justify his trajectory was that he was always a scammer and
           | was bidding his time, and just decided to take his scam and
           | build an aura of mystique around his... _condition_ as a
           | marketing ploy to justify the horrible thing he has built
           | that 's led to countless hacks. Hacks that I personally hope
           | are being used to fund more interesting and viable things,
           | because there is no way you can explain going from building
           | tools like dark wallet/market to crypto kitties and NFTs and
           | have it make any sense other than sheer grift.
           | 
           | With that said, I've worked with outreach programs to
           | reintegrate people on the severely incapacitated end of the
           | autistic spectrum: and I wouldn't wish that on anyone. To
           | live a life with no autonomy and have no real capacity to
           | communicate or to articulate your thoughts is perhaps the
           | worst type of hell I can think of as our very species 'Homo
           | Sapien' translates to Wise Man and often refereed to as a
           | _thinking monkey_ and they have been robbed of their very
           | Humanity.
        
           | swayvil wrote:
           | They may be assholes but gosh aren't they productive.
           | 
           | It reminds me of dwarves from Norse mythology. Short guys in
           | their little workrooms underground banging away at projects.
           | Grumpy. Making miraculous stuff. The shoe fits.
        
             | pingeroo wrote:
             | Very poetic way of putting it and I agree these are people
             | we certainly need! Wouldn't be writing this message if it
             | weren't for autism. But to some extent they are beasts of
             | burden.
             | 
             | Musk talks about his brain as if it's possessed by demons
             | sending him a million thoughts a minute. Not fun.
        
               | matheusmoreira wrote:
               | > But to some extent they are beasts of burden.
               | 
               | What? I'm sorry but I find that to be dehumanizing
               | towards people on the spectrum. They are human beings
               | like us.
        
               | swayvil wrote:
               | Ya, beasts of burden sounds right. Geese laying golden
               | eggs too. Destined for the egg factory.
        
               | Ygg2 wrote:
               | > his brain as if it's possessed by demons sending him a
               | million thoughts
               | 
               | Has he tried logging off?
        
             | rhexs wrote:
        
         | [deleted]
        
         | gremlinsinc wrote:
         | I have 'some autism' as in self-diagnosed a few years back when
         | someone else on the spectrum asked me flat out and said they're
         | certain I'm on the spectrum. It's funny I also have ADHD
         | (diagnosed at 38) and I watch youtube channels by people with
         | autism/adhd on how to cope, and a lot of the 'coping' skills or
         | masking things people do to fit in, I've organically discovered
         | on my own and have used just naturally since I was a kid.
         | 
         | Like, I couldn't stand being in class listening to the teacher,
         | I never ever listened, instead I just read ahead, guessed and
         | completed the homework assignment, and never had homework in
         | high school because of it.
         | 
         | My ADHD brain has kept me poor mixed w/ depression, but I feel
         | my logical autistic side sometimes balances it out, and makes
         | me think before doing something stupid/spontaneous.
         | 
         | Like I sometimes forget things, so I create rituals when I do
         | forget something, so I don't do it again. Example: I left my
         | keys in car back in 2003, had a bunch of latino guys helping me
         | in SLC try and break into my own car.
         | 
         | Since that day, I never turn the car off until I've got one
         | foot out the door, as a reminder the keys are still in ignition
         | because it's running. Lost my wallet once, and now I always put
         | it in the same pocket, and the same place at home when not in
         | my pants.
         | 
         | There's some things not great about autism, especially higher
         | up on the spectrum, but maybe evolution sometimes has hiccups
         | before it gets things right. Sometimes I think autism is more a
         | blessing than a curse, and there definitely are many great
         | minds who probably were on the spectrum.
         | 
         | It could be an evolutionary leap eventually, I hate how people
         | always call it a disorder or negative. Yeah, okay if you're
         | non-verbal or something yeah that's not great, but if you're
         | just very pithy when talking about a topic you're interested
         | in, and have a weird sense of humor (snarky redditors - as I'm
         | convinced reddit is literally the social network for autists),
         | and a little ocd but not clinically so, then it's not all bad.
         | 
         | ADHD on the other hand, I could really do without. I'm on
         | wellbutrin for depression which raises dopamine, and vyvanse
         | for ADHD which also raises dopamine, and my ability to focus
         | and get motivated has skyrocketed since I started it a few
         | months back, but before that my life was miserable. I'm making
         | 7k monthly now freelancing, I made 7k last year because I was
         | anxious, depressed, and had fatigue from long-covid.
         | 
         | I just had panic attacks even thinking about prospecting for
         | new clients. I had one good one but she was sporadic, and she
         | recommended me to my new client who's awesome and gives me 40+
         | hours per week. Though, I probably should raise my rates... I'm
         | a USA dev, freelancer with 10 years experience in laravel and
         | right now I'm doing django/python stuff and still only charging
         | $40 (same as I did like 4 years ago)... minimum wage has gone
         | up like $10 in a lot of places either by force, or by
         | competition.
         | 
         | It's amazing though what the right medical cocktail gets you.
        
           | supertofu wrote:
           | Are you a woman, by any chance? Autism diagnoses have
           | historically been very male-biased.
        
       | ThrustVectoring wrote:
       | So, a big thing about mental health diagnoses in general is that
       | they have two components: an identifiable behavioral difference
       | from neurotypical baseline, and enough difficulties and social
       | conflict in their life that mental health professionals end up
       | getting involved. The second part is important to keep in mind -
       | people who are like Bill Gross and wind up happily married and
       | running a highly successful bond fund simply do not get diagnosed
       | at nearly the rate as an eleven year old who cannot go through a
       | school day without a screaming meltdown.
       | 
       | This is especially important when it comes to identifying genetic
       | correlations with autism, since _anything_ that negatively
       | impacts overall functioning is going to wind up positively
       | correlated with autism diagnoses. Nobody sane is going to argue
       | that having an itchy skin condition means that you 're more
       | autistic, but an autist with itchy skin is more likely to have
       | enough behavioral issues in school to meet the threshold for a
       | mental health referral.
       | 
       | To summarize my point, there's all _sorts_ of genetic stuff that
       | will end up completely unrelated with _being autistic_ , but will
       | end up correlated with _getting diagnosed as autistic_. This is
       | because merely being neuro-atypical is not enough to get a mental
       | health diagnosis, you need to combine it with enough life
       | difficulties and social conflict to drive the bureaucratic
       | machinery involved with producing a diagnosis.
        
         | psychphysic wrote:
         | Excellent point well said.
         | 
         | It's part of why I find the neurodivergency movement likely
         | harmful.
         | 
         | It's the functional impairment that defines disease. Traits
         | which help classify the disease if one is present are present
         | in those without disease.
         | 
         | Shifting the definition from functional impairment to those
         | traits is not a good thing.
        
       | dzink wrote:
       | There may genetic propensity, but it may also be fueled by
       | maternal stress during pregnancy (anecdotally possibly energy
       | depravation of some kind or too high a cortisol level in the
       | blood). From Moms of multiples in FB groups, the level of anxiety
       | in each pregnancy in the same mom seems to result in similar
       | baseline anxiety in the baby. In one case a very early delivery
       | (27 weeks) in a mom with a very stressful professional
       | environment during pregnancy lead to the most severe case. Very
       | little seems to be done to investigate influence of stress,
       | different types of food intake, sleep on the fetus during
       | different pregnancies of the same parents.
        
         | nineplay wrote:
         | I have to wonder if maternal stress is on the rise in any
         | significant way. We can iterate though the list of stressors we
         | all have today, but for millennial mothers have given birth in
         | times war and famine and high infant mortality. Why would
         | autism be more common now than then.
        
         | callalex wrote:
         | Please, do not EVER try to come to any medical conclusions
         | based on observations of a Facebook mom group. That is
         | basically taking all of the known issues with anecdotes and
         | distilling it into a self-amplifying disaster.
        
         | upupandup wrote:
         | Maternal stress on the fetus has huge impact. In my mother's
         | case, before, during and after preganancy, she was abused,
         | starved (because my dad didn't want her to become fat), and
         | suffered all around. I believe this is what contributed to my
         | spectrum but I believe my dad also was on the spectrum but they
         | just didn't have the words to identify it back then. So it is
         | probably genetic mostly and environment also contributes.
         | 
         | Having said that its a big reason why I don't want children. I
         | don't want to pass this on to them, on top of the PTSD I
         | received from my dad and toxic environment.
         | 
         | I find it surprising that high functioning spectrum folks are
         | more likely to have offsprings than neurotypal. Because there
         | was a time when I wanted to start a family too.
        
       | jiggywiggy wrote:
       | Autism has been rising over the years.
       | 
       | Either it's been under diagnosed, or it's hard to believe it's a
       | purely genetic problem. Even though some people might be
       | susceptible to triggers. At the same time, something could be
       | messing up our DNA.
       | 
       | This article suggests, next to under & over diagnoising, late
       | parenting and obesity in moms.
       | 
       | https://www.verywellhealth.com/is-there-a-real-increase-in-t....
        
         | albertopv wrote:
         | Or maybe now is "over diagnosed". I met low functioning
         | autistic people and I consider them "real autistic", it's
         | almost impossible to have a social contact with them. I don't
         | think who call autism a "superpower" should be called autistic.
         | Or the way around, classification is a mess, autism class it's
         | too broad.
        
           | cpuguy83 wrote:
           | The existence of severe cases does not mean less severe cases
           | don't count.
        
             | spywaregorilla wrote:
             | Maybe. Calling it a spectrum is an accurate term, and thus,
             | pretty much everybody is on the spectrum. It's not a one
             | dimensional spectrum of course, but like... I'm probably a
             | high functioning aspie. Prone to obsessions, highly
             | temperature sensitive, didn't really grok some basic
             | aspects of socialization until I manually learned some
             | social rules in high school. But it's not severe enough to
             | be noteworthy and you wouldn't think anything was
             | categorically different unless you were thinking within
             | that framework already. Just a bit geeky really.
             | 
             | The issue comes in when people want to contextualize it as
             | a disease as an implied bad thing.
        
         | RobotToaster wrote:
         | I imagine it's heavily epigenetic.
         | 
         | In other words you need to have the genes for autism, but the
         | genetic switches (epigenetics) that control if a gene is on or
         | off need to be switched. Those switches are also sometimes
         | heritable.
        
         | ThrustVectoring wrote:
         | An autism diagnosis means that you're too autistic to function
         | in society without causing mental health professionals to be
         | involved in your life. There's at least two easily identifiable
         | non-genetic factors: society can lower the threshold of
         | autistic behavior that it tolerates, and mental health
         | professionals can be involved more often and at lower general
         | thresholds.
        
         | devwastaken wrote:
         | It's a largely U.S. problem, same with many other disorders.
         | The industrial era has put so many carcinogens into the air,
         | water, and food that there is bound to be changes.
         | 
         | Combine this with American culture of being unhealthy, and now
         | families are started far later in life - it's a "no duh"
         | situation.
        
         | marginalia_nu wrote:
         | I think public awareness is a pretty major contributor to these
         | "epidemics", often in synergy with media. We've had a lot of
         | autism-spectrum-type characters in the 00s and 10s. This speaks
         | quite loudly to the effect:
         | https://en.wikipedia.org/wiki/List_of_autistic_fictional_cha...
         | 
         | There is a lot more portrayals in the 2000s than before.
         | 
         | Without awareness of autism-spectrum disorders, someone on the
         | spectrum would probably have been considered shy, eccentric,
         | anxious, aloof, and/or a bit stupid.
         | 
         | There's previously been similar "awareness booms" with regard
         | to anxiety, depression, OCD and ADHD. This has roughly
         | coincided with the introduction of Xanax, SSRIs, Ritalin, and
         | so forth.
        
           | _jal wrote:
           | Dyslexia is another similar one.
           | 
           | And kind of similar is treatment of left-handed people - it
           | was routine through about the 70s to try to "correct" that.
        
             | marginalia_nu wrote:
             | Goes back a long way. It used to be the four temperaments
             | of melancholic, phlegmatic, sanguine and choleric were the
             | basis vectors for explaining human behavior. That's
             | absolutely a way you can reason about things.
             | 
             | Psychology, whether modern or ancient, creates a language
             | for speaking about our experiences and the behavior of
             | others, which shapes our way of thinking about it in an
             | almost Saphir-Whorf:ian way.
        
           | brippalcharrid wrote:
           | Some of these issues can also be clouded by the accomodations
           | that are put in place for them being perceived as incentives.
           | The impact of a diagnosis on school and university
           | examinations, for instance (eg. 25% extra time), is widely
           | recognized as being significant, and they are highly sought-
           | after as a result, with some people being more adept at
           | securing a diagnosis for their child than others.
        
             | ok_dad wrote:
             | There may be one or two parents who do this but trust me
             | that the process of seeking help for an autistic child is
             | not fun. I don't see how anyone can go through this for
             | those reasons, it's really hard emotionally.
        
         | FollowingTheDao wrote:
         | In very few cases it is purely genetic, like these de novo
         | cases they are finding, but the majority of cases are not.
         | 
         | I want to throw this out there, not as something I believe, but
         | as an idea to be discussed, that one factor in the rise of
         | Autism might be the sudden rise in wealth of a new type of
         | person (programmers, engineers, etc) which led to different
         | mating patterns and a sudden change in the genetics of the
         | children born to these couples. Or even just a change in how
         | they raise the kids and what food they eat.
        
           | MrPatan wrote:
           | Let's go back a bit and call it "the rise of the accountant".
           | I don't think there's been rich programmers in significant
           | numbers to for enough time to have moved the genetic needle
           | all that much.
           | 
           | But widen the category a bit and you'll find that the rewards
           | for a relatively obsessive attention to detail and being
           | comfortable with numbers have shifted in the past five
           | centuries or so, from a one way trip to the monastery (if you
           | were lucky) to a comfortable middle class life style, family
           | included.
        
             | FollowingTheDao wrote:
             | HA! I like that. But seriously, all it takes is one
             | generation for Autism to appear if the genetics for it are
             | present in the parents.
             | 
             | These people who were "accountants" were always working for
             | the rich, never rich themselves.
             | 
             | By the way, my father was an accountant (Went to NYU when
             | he was 16 back in 1951) and he later ended up working on
             | some of the first office computers. And here I am, being
             | told in my 50s that I am probably on the spectrum. My
             | mother was from a poor coal mining family in PA and she ran
             | away to NYC to find here way out of that life when she met
             | my father.
        
         | washbrain wrote:
         | Almost certainly undiagnosed. A similar thing happened when we
         | stopped stigmatizing left handedness. There was a sharp
         | increase in lefties over the next decade, then it leveled off
         | at whatever the natural point is.
         | 
         | I expect autism, depression, trans identities, lgb identities,
         | etc. are all things that are becoming more accepted and we're
         | going to see a sharp rise in them followed by them leveling off
         | at whatever the natural level is.
        
         | rogerkirkness wrote:
         | People with high functioning autism are more likely to have
         | children than neurotypicals, so there is some favourable
         | selection pressure as well.
        
           | supertofu wrote:
           | This is surprising. I would have assumed the opposite (people
           | with high functioning autism seem less susceptible to social
           | pressure to have children, and more likely to use birth
           | control, for example.)
           | 
           | Any guesses as to why?
        
           | MrPatan wrote:
           | The less strong claim is that people with functioning autism
           | reproduce more than they did before
        
           | alistairSH wrote:
           | Do you have a source for this claim? I'm not doubting you,
           | genuinely interested (my now-adult son is on the spectrum).
        
         | MrPatan wrote:
         | Why not both? How about modern world makes it easier for
         | autists to reproduce?
        
         | jklinger410 wrote:
         | As with every comment I write on this topic, there are surely
         | different disorders called "autism" that are being lumped
         | together. So their causes may actually be different.
         | 
         | If you leave a child alone with no human contact, it becomes
         | autistic very quickly. So there's definitely types of autism
         | that come from parenting.
         | 
         | But I would be shocked if autism at birth it is not being
         | caused by environmental pollution and low nutrition diets.
         | Which adds a tremendous body count on top of the already
         | monumental body count directly attributed to the FDA and EPA,
         | and the many political bodies that govern them.
        
           | callalex wrote:
           | You seem to be confusing your lack of understanding of ASD
           | with the scientific community's understanding of ASD. I'm not
           | even sure where to begin correcting you because your
           | understanding is fundamentally off.
        
           | spywaregorilla wrote:
           | > If you leave a child alone with no human contact, it
           | becomes autistic very quickly.
           | 
           | Citation needed. This is not accurate without some aggressive
           | hedging on what we're calling autistic. Lack of socialization
           | does tend to manifest in less social behaviors later on. And
           | less social behaviors are common among autistic people. But
           | that's not the same as saying lack of socialization causes
           | autism.
        
             | huetius wrote:
             | I think this poster has an axe to grind, but there is
             | definitely significant overlap between symptoms of child
             | abuse/neglect and early signs of ASD and other mental
             | disabilities. I am on mobile, and cannot right now give a
             | compact source, but the lists on Mayo etc. have a lot of
             | overlap.
        
               | spywaregorilla wrote:
               | There's also overlap between a stab wound and a heart
               | attack. You may say there's a cardiac related problem,
               | but you don't have a stab wound just because you have
               | some of the overlapping symptoms.
               | 
               | Neglect can cause a host of behavioral and neurological
               | issues but they're not autism. Medical literature
               | consensus is pretty clear on this. It was a popular
               | theory many decades ago. It's not held up to scrutiny.
        
           | jjallen wrote:
           | Aren't wealthier families more likely to have autistic kids?
           | Wouldn't this contradict your statement of environmental
           | pollution and low nutrition diets?
        
             | jklinger410 wrote:
             | I haven't seen the data around wealthier families. But
             | wealthier families have more access to healthcare and can
             | get earlier (and more thorough) diagnosis than poor ones.
             | So unless there was some kind of control for access to
             | healthcare, I would question that correlation.
        
               | alistairSH wrote:
               | This. We're relatively wealthy (typical middle management
               | salaries) and it took a string of doctor appointments
               | over many months to get a diagnosis for our son. Several
               | of these were multi-hour sessions. In addition to the
               | time off work to attend appointments, there was time on
               | the phone, time on the internet, time talking to school
               | counselors/teachers, scheduling IEP meetings at school,
               | and probably other stuff I've long since forgotten. There
               | wasn't a lot of out-of-pocket cash cost (because decent
               | insurance, not guaranteed in the US), but the time and
               | mental energy expended was significant on its own.
               | 
               | And, 100% anecdotal, but my wife's brothers both have
               | similar personality traits as our son. Neither was
               | diagnosed (and as far as I know, neither tested - this
               | would have been in the 70s and 80s). Both ended up as
               | typical middle-class, working-class Americans (own modest
               | homes, but no appreciable wealth beyond that).
        
             | brippalcharrid wrote:
             | It would at least appear that children from wealthier
             | families are being diagnosed with autism at a higher rate.
             | Perhaps pollution/nutrition is actually a dead end, or
             | maybe autism is less likely to be missed in the children of
             | wealthy parents, or perhaps diagnosis is more subjective,
             | enabling doctor-shopping, and there are perceived benefits
             | associated with a diagnosis. It would be interesting to
             | compare the rates of autism diagnosis amongst the children
             | of teachers and psychologists compared to
             | lower/middle/upper classes at large.
        
               | ljw1001 wrote:
               | It could also be that milder forms are an asset in an
               | information based economy
        
         | jmyeet wrote:
         | Don't underestimate under-diagnosis.
         | 
         | Over the last century the number of people who are left handed
         | rose from ~4% to ~12%. What happened? We stopped punishing
         | children for writing left handed and forcing them to write
         | right handed.
         | 
         | We like to blame this like autism and ADHD on emotional factors
         | like screen time. Maybe there's some truth to that. But I
         | firmly believe that a lot of neurodivergence can be explained
         | by better diagnosis and less punishment.
        
           | jiggywiggy wrote:
           | Dont underestimate over diagnosing in these overbearing
           | times.
        
         | emmelaich wrote:
         | I can believe it's mostly genetic; in these days of social and
         | geographical mobility you're more likely to mate with someone
         | in the same industry rather than say your high school
         | sweetheart.
        
           | FollowingTheDao wrote:
           | And more likely to mate with someone with a different
           | cultural background, which has a greater impact on our
           | genetics.
        
       | davidf18 wrote:
        
       | londons_explore wrote:
       | Assuming these genetic causes fully explain autism (ie. there are
       | no environmental factors), does that suggest that the percentage
       | of the population with autism has remained approximately constant
       | throughout recent history because it is caused by random
       | mutations?
        
         | stu2010 wrote:
         | This paper is looking at both inherited genes, that is genes
         | that you get from your parents, and de-novo mutations, that is
         | a mutation that only the offspring has, that wasn't directly
         | copied from a parent.
         | 
         | We've known for a while that autism is highly heritable. This
         | paper builds on a large body of work that links specific genes
         | to autism's heritability. I haven't dug into the specific
         | breakdown, but my understanding is that a majority of genetic
         | variants associated with autism are inherited, rather than the
         | random de-novo (new) mutations.
        
         | autosharp wrote:
         | No. All mutations are random. In the past, ASD might have been
         | more or less adaptive than it is today.
        
           | FollowingTheDao wrote:
           | To be clear, mutations are random, but polymorphisms are not.
        
         | bena wrote:
         | Here's a fun one. We will never know how common dyslexia was
         | throughout history.
         | 
         | Literacy is recent. In the 1970s roughly 35% of the population
         | was still illiterate. Go back further and you're looking at 10%
         | or less. Most signs were pictorial. A blacksmith was denoted by
         | an anvil, a tailor by a spool and needle, etc.
         | 
         | If you were dyslexic, you'd never know.
         | 
         | Autism is likely in a similar boat. Those individuals with less
         | disruptive traits could probably find themselves doing well.
         | Possibly joined the priesthood where they can apply their focus
         | creating manuscripts. Or become hermits, where they could live
         | somewhere less stimulating. Whereas those individuals with
         | highly disruptive traits were probably treated quite poorly.
         | Crammed into sanitariums or confined to monasteries to exorcise
         | whatever evil spirit may have possessed them. Or simply died
         | from being rejected by their families.
         | 
         | We can't really know. We can probably safely assume that while
         | our knowledge of autism is new, it itself is not new.
        
         | atwood22 wrote:
         | There is a correlation between the father's age and ASD. People
         | are having kids older now, so the answer is no, it's unlikely
         | that the percentage of people with ASD is constant throughout
         | history.
        
       | jklinger410 wrote:
       | Very cool to identify that "autism" is genetic. But I'm certain
       | that there is no such thing as "autism" but a varying set of
       | disorders with vaguely similar symptoms.
       | 
       | So there could be one kind of autism that is 100% genetic and the
       | rest are 0% genetic. But we don't know, because we are still
       | lumping them together.
        
         | alistairSH wrote:
         | _But I 'm certain that there is no such thing as "autism" but a
         | varying set of disorders with vaguely similar symptoms._
         | 
         | That's the definition of autism, so you'd be correct. Autism is
         | a diagnosis of the symptoms, not any particular cause. And a
         | diagnosis covers a wide array of symptoms (often related to
         | social interaction, but not always), of which any particular
         | person might only have a few.
        
           | jklinger410 wrote:
           | I think we are mostly agreeing, but let me be specific here.
           | The NIH starts by defining autism:
           | 
           | "Autism spectrum disorder (ASD) is a neurological and
           | developmental disorder."
           | 
           | Defining autism as a DISORDER rather than common symptoms
           | caused by a myriad of different disorders is where the issue
           | is. I know we're doing a semantics game here, and doctors may
           | full well understand this, but the public does not.
           | 
           | Then further:
           | 
           | "Autism is known as a "spectrum" disorder because there is
           | wide variation in the type and severity of symptoms people
           | experience."
           | 
           | Again, the spectrum is being defined as a variation of
           | symptoms (with an implied common disorder), not a variation
           | of disorders with similar symptoms.
           | 
           | Am I misunderstanding the word disorder here?
        
             | alistairSH wrote:
             | No, you're not misunderstanding the word disorder. Autism
             | encompasses a greater degree of heterogeneity than most
             | other disorders. At some point in the future, we may very
             | well break autism into several distinct sub groups. But at
             | this time, efforts to do so have mostly failed. The removal
             | of Asperger's as a separate disorder being an example of
             | this difficulty.
        
         | hunta2097 wrote:
         | My son has autism and through his schools and colleges I have
         | known 100s of "autistic" kids and young adults. There is such
         | variety in their traits and behaviours.
         | 
         | I honestly don't find the label useful, I would say I am
         | getting increasingly annoyed by it.
         | 
         | There should be more work done on sub-classifications and
         | grouping of different sub-conditions.
        
           | alistairSH wrote:
           | _There should be more work done on sub-classifications and
           | grouping of different sub-conditions._
           | 
           | Interesting that you say that, as recently, society has moved
           | in the other direction (dropping Aspergers as an independent
           | diagnosis, instead lumping it in with ASD, for example).
           | 
           | As another parent of an autistic son, I at least partly
           | agree. The label "autism" on its own is mostly useless. The
           | individual symptoms are much more useful to identify and work
           | around/treat. But, that would just leave you with a laundry
           | list of things to write/say/describe, so also of limited
           | value outside medical/professional contexts.
           | 
           | "He's autistic" vs "He has a severe executive functioning
           | deficit, moderate OCD, mild ADD, stims in this particular
           | way, and doesn't make eye contact with strangers."
        
           | jklinger410 wrote:
           | As someone who has family with mid to low functioning autism,
           | I find the label mix ups to be absolutely infuriating.
           | 
           | When someone calls autism a "superpower" I have to leave the
           | environment or log off before I say something awful.
        
             | hunta2097 wrote:
             | Yeah, i'm glad someone else finds that as infuriating as I
             | do!
             | 
             | "it's a spectrum" is just a lazy out, there needs to be
             | proper classification or we are never going to get further
             | with diagnosis and treatment.
        
               | axus wrote:
               | "political spectrum" is a term that frames viewpoints on
               | a line from "good" to "bad", when actually there are so
               | many political issues that the number of dimensions makes
               | it hard to call it a spectrum.
               | 
               | Electromagnetic waves are an actual spectrum, if you only
               | look at the frequency.
        
           | PragmaticPulp wrote:
           | > I honestly don't find the label useful, I would say I am
           | getting increasingly annoyed by it.
           | 
           | The exact same thing is happening to Long COVID:
           | 
           | A small number of people are truly devastated by post-COVID
           | issues that can last for years (or more, we don't know yet).
           | 
           | A much larger number of people have some milder post-COVID
           | issues that can linger for months or longer, but don't
           | otherwise wreck their life.
           | 
           | The problem is that both groups are being lumped into the
           | "Long COVID" description, which is a huge disservice to those
           | severely debilitated by post-COVID issues. It's getting so
           | bad that a lot of people don't believe Long COVID can be a
           | serious issue because everyone they've seen with "Long COVID"
           | has relatively mild symptoms and they're just not seeing the
           | more rare Long COVID sufferers who have serious issues.
           | 
           | We really need to stop lumping mild and serious conditions
           | under the same label
        
             | thewebcount wrote:
             | > A small number of people are truly devastated by post-
             | COVID issues that can last for years (or more, we don't
             | know yet).
             | 
             | I would argue that we _do_ know, but that the instances of
             | it are so stigmatized that doctors and the media are blind
             | to it. Other diseases like POTS, MCAS,  & EDS seem to have
             | a lot in common with long COVID and look to me to be
             | basically the same thing triggered by a different virus.
             | 
             | My spouse has suffered from them for about 12-15 years now.
             | It's particularly infuriating because there are even
             | clinics set up for studying and treating long COVID for all
             | the symptoms she has, but she isn't allowed in them because
             | she's never had COVID. Hers definitely appears to have
             | started after getting mono as a teenager. She was hit
             | really hard, but after about 6 months was back to normal.
             | Then in her late 30s it hit her and now she can't work or
             | do much of anything. When she stands up, her heart rate can
             | go up to 130bmp just standing and doing nothing. She starts
             | to white out, but unlike some doesn't actually pass out,
             | which may actually be worse.
             | 
             | It's actually kind of a relief to have a large group of
             | people very visibly get the same symptoms in a way that
             | makes it much harder to dismiss as anxiety or depression.
             | Hopefully if anything good comes out of COVID it will be
             | that long COVID-like diseases will be studied and better
             | understood.
        
       | itsthemmrvax wrote:
        
         | nickmyersdt wrote:
         | AFAIK all credible studies into the link between MMR vaccine
         | and autism have concluded that there is no link, do you have
         | new information?
        
           | itsthemmrvax wrote:
        
         | sovnade wrote:
         | sigh. there are dozens of easily viewable meta-analyses of
         | millions of children that show no link, and zero that do.
        
           | philliphaydon wrote:
           | While I don't believe there is any link. I've always found it
           | strange that the US bundles SO many vaccines together in a
           | shorter period of time compared to NZ/AU/UK.
        
             | shagie wrote:
             | The CDC page on the bundling of vaccines which goes quite a
             | bit into the why of it -
             | https://www.cdc.gov/vaccines/parents/why-
             | vaccinate/combinati...
        
             | wahern wrote:
             | AFAIU, combined vaccines are preferred in the U.S. because
             | we have problems with compliance, scheduling, and follow-
             | up, especially in at-risk communities. Minimizing the
             | number of appointments this way is a simple technological
             | workaround to deeper sociocultural issues. Other countries
             | may have similar problems, but the U.S. has a habit of
             | leaning on technological solutions, for multiple reasons
             | but in no small part because we're crazy rich and _can_ ;
             | whereas some other countries are more predisposed to low-
             | tech, behavioral remedies.
        
               | philliphaydon wrote:
               | Makes sense. Thanks.
               | 
               | And thanks for the link in the other reply.
        
           | t0bia_s wrote:
           | Link please. I want to see studies that proofs that there are
           | autism diagnosed unvaccinated people in our population.
        
       | washbrain wrote:
       | Interesting. Now I'm wondering if I can check my own genome from
       | data from 23&me to see if I have any unusual variants.
        
         | farresito wrote:
         | If you really are interested in that, I would suggest you skip
         | 23andMe entirely and get your whole genome sequenced. That's
         | where the actually interesting stuff is. That's where you will
         | find the high risk variants.
        
       | upupandup wrote:
       | I just finished watching Extraordinary Attorney Woo Young Woo and
       | while there are exaggerations, it has been a delightful show in
       | highlighting the struggles of those on the spectrum.
       | 
       | In particular these quotes stand out:
       | 
       | "People on the spectrum have a pattern of rigidity and repeated
       | behaviors"
       | 
       | "Don't answer questions that wasn't asked, don't do anything that
       | you weren't asked to do"
        
       | kaiusbrantlee wrote:
       | Correlation does not equal causation
       | 
       | Its amazing how many supposed experts skip right over that. JFC.
       | 
       | IOW, the gene mutations could be a response, not a cause.
        
         | peteradio wrote:
         | Correlation is nearly always the first step in identifying a
         | causality.
        
           | upupandup wrote:
           | Unfortunately anybody who spent money attaining low level
           | Bachelors degree goes around repeating that phrase. It's
           | meant to shut down any discussion and signals pedantry.
           | 
           | It's the equivalent of "X is not a reliable source, therefore
           | I reject all claims by X" people use to shut out anything
           | that threatens their perception of reality.
           | 
           | I hate it. It's rampant on HN and reddit.
        
             | amanaplanacanal wrote:
             | The assumption that "is associated with" is the same as
             | "causes" is also rampant. It's good to be reminded that
             | causation could flow either way, or that a third thing
             | could be the causative factor.
        
               | dekhn wrote:
               | This is the difference between genetics and molecular
               | biology. In most cases, genetics treats gene function as
               | an abstraction while molecular biology seeks the
               | underlying mechanistic process by which genes and their
               | products function (this is an oversimplification).
               | 
               | There is a long history of discovering genes associated
               | with diseases and then determining the molecular
               | etiology/mechanism of the disease. In the case of autism
               | we often see gene associations which seem fairly obvious-
               | for example genes that encode for the proteins that make
               | neural pathways- but sometimes also other genes which
               | woudln't seem related at all or are more "general" and
               | would affect people in many ways- a motor protein that
               | carries things from one part of the cell to another- can
               | be associated but it's challenging to build a true causal
               | model.
               | 
               | From having worked in this field some time, the
               | relationship between a human genotype and their body-
               | level disease phenotype is an extraordinarily complex
               | one, with huge amounts of nonlinear terms. Pretty much
               | the only reasonable way to deal with this right now is to
               | build deep models and feed them enough data to build rich
               | representations with predictive ability. Embeddings and
               | transformers have recently been shown to be remarkably
               | successful in this area.
        
         | svnt wrote:
        
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