Integrating variants in 42k autism cases identifies mutations in new genes
nature.com
nature.com
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.
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.
Claiming to have autism with no detectable impairment is like me claiming to be blind because despite having 6/6 vision (i.e. normal) because that's is actually worse than average vision for my age group (6/5 is average healthy young adult vision).
It would be interesting to see, of the people that share these de-novo mutations, who have the genotypes, but not the phenotypes – or see if some people have been treading water as undiagnosed autistic their whole life and give them some insight as to why navigating a neurotypical world is so difficult for them.
The nature of health care also means that some of these conditions are "middle class" diseases, meaning that if you have the money to spend you can get diagnosed more quickly. There is some evidence of abuse of this, where wealthy parents get their children diagnosed in order to get school exams re-taken, etc. In general though, the diagnoses are spreading from the most severe to the middle of the range.
For those neurodiverse who can manage reasonably well in society by presenting well behaviourally, knowing ones own neurotype can be incredibly helpful, even if you do not take any further action after the diagnosis.
1. https://www.statista.com/statistics/252393/total-us-expendit...
How does one going about finding their neurotype?
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....
Any guesses as to why?
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.
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).
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.
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.
Nobody said this was true for autism. Only that resulting misdiagnoses may be contributing to the uptick.
> 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.
Autistic children are born not caring for faces, or eyes, and social interaction. Feral children do not have eyes or faces or social interaction to look at. So if it's not technically autism, it's not any different than the myriad of disorders currently lumped together as autism.
Since you seem to have no opposition to using personal definitions of things based on personal opinions without feeling the need to clarify, I'm glad you agree with me 100%
In this case, to be clear, pudding means productive.
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.
And kind of similar is treatment of left-handed people - it was routine through about the 70s to try to "correct" that.
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.
On the other, I see it as a sign of societal progress and even decadence. Compared to all the other ways people can be defective, these mental issues are pretty low-stakes. If depression and anxiety are occupying this much of our mindspace, there must not be bigger problems to worry about.
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.
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.
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.
The issue comes in when people want to contextualize it as a disease as an implied bad thing.
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.
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.
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.
Combine this with American culture of being unhealthy, and now families are started far later in life - it's a "no duh" situation.
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.
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.
When someone calls autism a "superpower" I have to leave the environment or log off before I say something awful.
"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.
Electromagnetic waves are an actual spectrum, if you only look at the frequency.
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
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.
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."
Even as a neuro-divergent (and very likely autistic, but not diagnosed) person I struggle to understand my actually diagnosed autistic childrens' (plural) experiences.
One thing I think is fairly common is the sensitivity to pain (physical or emotional) is typically much stronger to the point of trauma that would be nothing for a "neurotypical". Whether or not that trauma is expressed outwardly (or in a specific way) varries greatly from person to person.
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.
"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?
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.
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"
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.
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.
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.
Sometimes I think that refutation is inherently more attractive than discussion or support. What you think?
"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.
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.
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.
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.
Musk talks about his brain as if it’s possessed by demons sending him a million thoughts a minute. Not fun.
Has he tried logging off?
What? I'm sorry but I find that to be dehumanizing towards people on the spectrum. They are human beings like us.
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.
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.
It's not complicated at all and a lot of it can be done with basic Linux tools, like grep, and visualized with CSV viewers like Visidata. That's just a basic explanation. If you end up getting your genome sequenced and want to analyze it, let me know in a comment.
Its amazing how many supposed experts skip right over that. JFC.
IOW, the gene mutations could be a response, not a cause.
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.
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.