I had Todd Lencz as a teacher and research track mentor--he's a mensch. I also have a very close friend with schizophrenia, many patient with the disorder, and a family history replete with psychiatric illness. Beware what you wish for--you can screen your embryos all you like and still have a kid who is a real A-hole. Or a magical child who happens to have schizophrenia. Or any number of other outcomes. If we create a more decent world, with less stigma and better treatments, we can spend less time fretting over our woeful genes and spend more time on woeful behaviors of the humans and systems that make schizophrenia so bad to have in the first place.
Let me express my appreciation for these posts by Awais Aftab (and Scott Alexander) about polygenic screening and schizophrenia. The posts are so densely argued, fair minded, data-driven...
I am loosely affiliated with the psychiatry residency program at UCSF, and I'm feeling like telling the department, hey, time to include material like this in the program...
I think a lot of this is double-counting. You mention that the reduction in relative risk is supposedly 40-50%, but that also you need to consider [all the factors that make it only 40-50%, and not 100%]. For example, unless I'm very confused, Orchid's calculator already uses the likely spread of embryos in a given family.
I'm skeptical of worrying too much about future environmental changes. For one thing, we know that Neanderthals had a higher polygenic risk for schizophrenia than moderns, presumably because evolution has been selecting against it since then. This suggests the polygenic structure of schizophrenia is still identifiably similar to what it was in Neanderthal times. But also, future environmental changes can make genetic predictability go down *or* up. For example, in general, as living standards rise, more of the risk for a condition becomes genetic (because you solve the most pressing causes of environmental risk, eg pollution or malnutrition). I don't think this kind of issue would normally rise to our attention.
The fact that you can select for many conditions at once makes polygenic screening strictly *better* than if you couldn't. That is, you always have the option to just select against schizophrenia and nothing else. If you're selecting based on other things too, it must be because you decided that was an improvement over just selecting against schizophrenia. I don't think this is reasonably considered a point against polygenic screening's efficacy.
I think the "diminish as much as possible" scenario is a Bad End, in that schizotypy seems really intertwined with something important that's like "willingness to entertain unusual ideas", or "lack of kneejerk conformity", or "zetetic Pyrrhonism". It...really worries me! I don't think a world in which it were the case would have much value or be worth living in.
(This is not quite synonymous with a simple 'schizotypy-creativity' connection.)
One thing that stands out to me is the particular way the schizophrenia/educational attainment paradox shakes out, as discussed by Lam et al. (2019):
A pretty simple model of "educational attainment" PRS (aside: I love using the "risk" acronym for things people generally agree are good) suggests it's a mix of "intellectual ability", "diligence", and "intellectual curiosity". #3 is a huge part -- we tend to think of "intellectual curiosity" as something basically coterminous with intelligence, but the correlation between "score on Intellect/Imagination scales" and "score on IQ tests" is very weak! Intellect/Imagination is only one component of how "Openness to Experience" is measured, so we wouldn't expect the correlation between "this pure aspect" and "Openness" to be anywhere near perfect, but we'd expect it to exist. #2, the diligence-type-thing, should load on Conscientiousness.
The "educational attainment paradox" in schizophrenia genes is positively correlated with Openness and negatively correlated with Conscientiousness. This really suggests it's the "purest" possible version of the "intellectual curiosity" measure -- what's left over when you completely negate all benefits from "intellectual ability" and "diligence". I take the position that intellectual curiosity is good and should be more common.
I had Todd Lencz as a teacher and research track mentor--he's a mensch. I also have a very close friend with schizophrenia, many patient with the disorder, and a family history replete with psychiatric illness. Beware what you wish for--you can screen your embryos all you like and still have a kid who is a real A-hole. Or a magical child who happens to have schizophrenia. Or any number of other outcomes. If we create a more decent world, with less stigma and better treatments, we can spend less time fretting over our woeful genes and spend more time on woeful behaviors of the humans and systems that make schizophrenia so bad to have in the first place.
Let me express my appreciation for these posts by Awais Aftab (and Scott Alexander) about polygenic screening and schizophrenia. The posts are so densely argued, fair minded, data-driven...
I am loosely affiliated with the psychiatry residency program at UCSF, and I'm feeling like telling the department, hey, time to include material like this in the program...
I think a lot of this is double-counting. You mention that the reduction in relative risk is supposedly 40-50%, but that also you need to consider [all the factors that make it only 40-50%, and not 100%]. For example, unless I'm very confused, Orchid's calculator already uses the likely spread of embryos in a given family.
I'm skeptical of worrying too much about future environmental changes. For one thing, we know that Neanderthals had a higher polygenic risk for schizophrenia than moderns, presumably because evolution has been selecting against it since then. This suggests the polygenic structure of schizophrenia is still identifiably similar to what it was in Neanderthal times. But also, future environmental changes can make genetic predictability go down *or* up. For example, in general, as living standards rise, more of the risk for a condition becomes genetic (because you solve the most pressing causes of environmental risk, eg pollution or malnutrition). I don't think this kind of issue would normally rise to our attention.
The fact that you can select for many conditions at once makes polygenic screening strictly *better* than if you couldn't. That is, you always have the option to just select against schizophrenia and nothing else. If you're selecting based on other things too, it must be because you decided that was an improvement over just selecting against schizophrenia. I don't think this is reasonably considered a point against polygenic screening's efficacy.
I think the "diminish as much as possible" scenario is a Bad End, in that schizotypy seems really intertwined with something important that's like "willingness to entertain unusual ideas", or "lack of kneejerk conformity", or "zetetic Pyrrhonism". It...really worries me! I don't think a world in which it were the case would have much value or be worth living in.
(This is not quite synonymous with a simple 'schizotypy-creativity' connection.)
One thing that stands out to me is the particular way the schizophrenia/educational attainment paradox shakes out, as discussed by Lam et al. (2019):
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699140/
A pretty simple model of "educational attainment" PRS (aside: I love using the "risk" acronym for things people generally agree are good) suggests it's a mix of "intellectual ability", "diligence", and "intellectual curiosity". #3 is a huge part -- we tend to think of "intellectual curiosity" as something basically coterminous with intelligence, but the correlation between "score on Intellect/Imagination scales" and "score on IQ tests" is very weak! Intellect/Imagination is only one component of how "Openness to Experience" is measured, so we wouldn't expect the correlation between "this pure aspect" and "Openness" to be anywhere near perfect, but we'd expect it to exist. #2, the diligence-type-thing, should load on Conscientiousness.
The "educational attainment paradox" in schizophrenia genes is positively correlated with Openness and negatively correlated with Conscientiousness. This really suggests it's the "purest" possible version of the "intellectual curiosity" measure -- what's left over when you completely negate all benefits from "intellectual ability" and "diligence". I take the position that intellectual curiosity is good and should be more common.