[NeuroCoder]

It's important to note that models that use genome wide association analysis have demonstrated extremely high predictive value across large cohorts sharing geography but are very poor when applied on a geographically distinct population. This suggests that although autism has a strong association with genetics, neurophysiology unique to autism develops in the context of highly complex genetic associations that are likely subject genetic drift across population and time.

When we have a a few genes of interest that are important in screening for a rare disease we accept that novel variants will continue to be identified throughout the years as more people are screened. Autism as a prevalence of 1-3%. I don't remember the exact number but I think something like 30% of autism diagnoses are believed to be secondary to fairly severe but distinct genetic syndromes. So when we talk about a subgroup of autism without clear etiology we are looking at a fraction of 70% of 3% of the population. We're approaching rare disease territory when we talk about subgroups within autism. A rare disease with a highly complex genetic association across the genome that is subject to genetic drift is not a good candidate for genetic screening.

All that being said, studies like this may provide valuable insight into what microbiology is being influenced, even if we can't reliably predict which variants are responsible. Id love to see future investigations relate genetics to biomarkers instead of behavioral tests in autism.

[maeil]

Did GPT help you write this, or do you just happen to write in the same style, conditioned by having to write research literature in that style?

[NeuroCoder]

It's the latter plus typing on my phone while riding the bus.

[ruthmarx]

> This suggests that although autism has a strong association with genetics, neurophysiology unique to autism develops in the context of highly complex genetic associations that are likely subject genetic drift across population and time.

Wouldn't it be more likely local culture and brain plasticity are the cause of these differences?

[NeuroCoder]

Autism can be reliably diagnosed at 2.5 years of age, so we probably aren't looking at a strong cultural bias in in how kids are presenting with autism. These models using data from countries where the healthcare systems provides support for appropriate screening and testing further minimizing bias due to culture. In other words, one would not expect these models to be overfit to phenotypically distinct representations of autism as a result of culture.

Variations in brain plasticity have been suspected of playing a role in autism for a long time. Brain plasticity may vary by region, throughout development, and at a molecular level. If population dependent variations in plasticity are indeed responsible for the lack of model generalizability, then the next step would be to do as I previously suggested. That is, identify where the many genome wide variations converge on biomarkers driving differences in plasticity.