This "older parents" hypothesis is thrown around very often, but it's entirely based on correlational studies (obviously, it wouldn't be ethically possible to do it in a controlled study).
And there's a very plausible alternative explanation for that correlation: Autism is probably at least partly genetic and autism impacts social interaction. It's very plausible to think that it simply takes people with autistic personality traits longer to find a partner to have children.
No, its also based on the fact that older parents (and especially fathers) lead to more de-novo mutations (which you can already see in sperm) and in this study now they show that especially de-novo mutations play a role.
If the older parents hypothesis was not true, you would not find higher autism rate is younger siblings or how do you account for that in your alternative explanation?
But sure, as they say in the paper, its most likely not a single large effect variant that causes autism but usually the combination of multiple rare variants. The genetically inherited part may also play a rule. For a complex disease such as this, its not a single cause that is responsible even for one patient. A tall basketball player can be tall due to some luck, tall parents and good nutrition all at the same time.
> The hypothesis that autism risk in offspring is positively associated with high parental intelligence, and high socioeconomic status, traces to Kanner (1943, p. 248), who stated, referring to autistic children, that “they all come of highly intelligent families,” at high levels of educational, socioeconomic and occupational achievement (Kanner and Lesser, 1958; Rimland, 1964). King (1975) reviewed a set of demographic studies motivated by these findings, and reported strong support for the pattern of high socioeconomic status linked with autism, including support from studies (e.g., Lotter, 1966, 1967) that checked all young children (of 8–10 years) in a given geographic area for infantile autism, and thus should be largely independent of confounding ascertainment or help-seeking biases, variation in access to relevant health care, or variation in parental awareness.
Note that these observations are 60+ years old. Read the entire "Socioeconomic status" section of the paper I cite. They argue the same and state genetic testing should be done to back it up. These seems an ideal study for 23andme (yes, yes, I know how a vocal minority feels about this org).
I guess what I'd like to know is (and I'm specifically asking you because you seem to be knowledgeable):
1. It sounds like de-novo mutations are the best theory for 70%+ of autism cases per this paper, right?
2. Does anybody track the "base rate" of de-novo mutations / generation in humans? If so, how many generations back do we have data for, and how many regions?
3. Aren't we seeing an increase in autism is developed nations even within poor uneducated families with young parents?
One study says ~38 individual base mutations per generation, but that increases by about 2 bases per year of the father's age, which is still not much given 6 billion base pairs in humans. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548427/) These studies, however, are missing rearrangements and other spontaneous structural changes which might not modify the genes at all but might change their expression or dosage. We don't have enough data yet about structural mutation rates, the technology to assess that at scale and low cost is only coming online now. Not sure about the incident rate, but since the guidelines for reporting have widened so much in the last decade that might mask any ability to really know.
