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Small-Scale Question Sunday for June 23, 2024

Do you have a dumb question that you're kind of embarrassed to ask in the main thread? Is there something you're just not sure about?

This is your opportunity to ask questions. No question too simple or too silly.

Culture war topics are accepted, and proposals for a better intro post are appreciated.

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My wife and I are looking to start having children shortly. As you might imagine being dual-income professionals, we left it to somewhat later in life (32 for me, 30 for her). I was diagnosed as a child with Asperger's Syndrome (now high-functioning or Level 3 autism, I believe), and her brother is severely disabled with low-functioning autism (she also has a lot of the classical traits, but was never diagnosed).

I've been scouring the internet for the last few hours but haven't found anything useful in terms of research - is there anything out there talking about the chance of having low-functioning autistic kids if you're high-functioning yourself?

We're tossing up going down the IVF route, maybe taking a trip to Greece and getting female embryos implanted to avoid the worse outcome, but it's difficult to make that call without knowing the odds.

If you're going the IVF route seriously consider getting your embryos screened for autism via Orchid genomics. It costs about $1200 per embryo but can easily save you hundreds of thousands in money and emotional worry from having to deal with an autistic child for life.

No links to Orchid, they're just the only ones I know who do polygenic screening for tism at the moment.

They do now? Nice, didn't know that.

Unfortunately "low functioning" has become a bit of a no-no term, everyone is either "high functioning" or just has autism (which still includes plenty of "medium functioning"). There's a few newish papers using the term, but most are older, and none are about what we are interested in.

But as usual in science, you can read between the lines. Generally speaking, autism is nowadays considered a continuous range of impairment, literally called ASD (autism spectrum disorder). One of the more popular ways to measure it is the social responsiveness score (SRS), which is then transformed into the SRS T-score (corrected for age, gender etc. similar to how IQ isn't just a raw test score but normed to 100). The T-score is normed to 50 with an SD of 10, so 60- is normal, 60+ mild, 65+ medium, 75+ severe. There's also quite a few other measures, but understanding at least one makes reading the papers a lot easier.

I'd say the closest to what you want to know is the heritability of these quantitative traits (1,2). TL;DR: the SRS T-score is moderately to highly heritable, in fact most measures of ASD severity are. In particular, I'm a big fan of monozygotic vs dizygotic twin comparisons since they sidestep many of the usual complaints, which in this case leads to a high heritability estimate of ~56-95%. There's a few other concepts you can take a look at, such as familial risk (which often don't include a measure of severity, only an ASD yes/no which is imo outdated at this point) or autism prs scores, but the results are mostly consistent between them.

So, in short, your children will most likely have an autism level similar to your own, with maybe a slight correction towards the mean and with a significant variance. Which necessarily implies a substantially increased chance of severe outcomes given the continuous nature of the disease. Exact numbers are difficult to give without knowing more, sorry. But chances of 10% and upwards, depending on where you make the cutoff of what you consider sufficiently problematic, aren't implausible.


On a sidenote, my favorite approach is measuring the degree of relatedness between siblings (for those that don't know, siblings, unlike parent-offspring pair which always get almost exactly 50% of each parent, can in theory range from 0-100% in genetic relatedness depending on which part of the parent's genome they get, though in practice it's a normal distribution around 50%) and then measuring the heritability based on that. Since this is doable for the majority of society, it further sidesteps some complaints about twin and/or adoption studies such as non-generalisability or different treatment between obviously different siblings.

I appreciate this greatly - I'm going off to do some more reading and we're going through the SRS together to try and figure out where we might sit and what that heritability might look like. Given the chances at play, $20-30k for a few rounds of IVF for gender selection doesn't seem very unreasonable at all, but I'll start drilling down into the numbers a little more.

As an aside - ultimately my concerns are more about nonverbal children requiring constant care. We make the sort of money that a child being mostly homebound or unable to work but mostly functional is within the risk we're willing to take, but we won't make that kind of money if we're suddenly in full-time caring roles.

What does gender selection have to do with it?

Autism is ~4x more prevalent in boys than in girls. This is true for a lot of genetic diseases due to the relative size of the X chromosome meaning girls can have one copy of a allele that causes issues and have it 'error-checked' so to speak by the other.