Yes, I hear criticisms like those made by your friend all the time. They aren’t particularly discouraging to me.
The variation is not that much lower. The standard deviation of any continuous trait is about 70% that of the general population. That’s still plenty for selection.
The impact from rare genetic variants is mostly NOT captured in today’s genetic predictors, and that’s a place where the field could improve more in the future. But you don’t NEED rare genetic variants for embryo selection to work. You just need a predictor that correlates strongly enough with the actual trait for selection. And for many traits we already have that.
The paper you linked showing heritability is lower using relatedness disequilibrium regression was interesting. They don’t include intelligence or most of the disease predictors on which embryos are currently selected in the table, so it’s hard to give a good estimate of how strongly we should expect it to affect future increases in the efficacy of embryo selection.
If I just kind of blindly extrapolate based on the heritability of height in their study and what I know about the heritability of height vs intelligence in other studies, I conclude that the RDR method would generate an estimate of the heritability of intelligence of about 35-40%, which sounds pretty low, but not absurd.
It seems pretty likely we could still get a predictor that explained 30% of variance in the trait just using SNP arrays and large sample sizes, so my estimate of the efficacy of embryo selection for intelligence in the future doesn’t change much based on that.
The supplement is mostly a verbal argument along the lines of “there are just huge number of rare variants, each of which exists in only a few people, so it will be difficult to figure out how to use them to improve phenotype prediction.”
This is true, but from everything I’ve read this seems to not matter that much for one simple reason: rare alleles with small effects don’t account for that much of the variance in trait values. Like if the RDR method’s estimate of heritability is accurate for height, we should expect rare variants to raise the variance explained from 45% to 55%, which would result in a ~10% increase in expected height if you were selecting embryos based on that trait.
That would be nice, but it’s not necessary for embryo selection to work.
If your friend wants to talk about this more I’d be happy to have a conversation with them.
Yes, I hear criticisms like those made by your friend all the time. They aren’t particularly discouraging to me.
The variation is not that much lower. The standard deviation of any continuous trait is about 70% that of the general population. That’s still plenty for selection.
The impact from rare genetic variants is mostly NOT captured in today’s genetic predictors, and that’s a place where the field could improve more in the future. But you don’t NEED rare genetic variants for embryo selection to work. You just need a predictor that correlates strongly enough with the actual trait for selection. And for many traits we already have that.
The paper you linked showing heritability is lower using relatedness disequilibrium regression was interesting. They don’t include intelligence or most of the disease predictors on which embryos are currently selected in the table, so it’s hard to give a good estimate of how strongly we should expect it to affect future increases in the efficacy of embryo selection.
If I just kind of blindly extrapolate based on the heritability of height in their study and what I know about the heritability of height vs intelligence in other studies, I conclude that the RDR method would generate an estimate of the heritability of intelligence of about 35-40%, which sounds pretty low, but not absurd.
It seems pretty likely we could still get a predictor that explained 30% of variance in the trait just using SNP arrays and large sample sizes, so my estimate of the efficacy of embryo selection for intelligence in the future doesn’t change much based on that.
This is true, but from everything I’ve read this seems to not matter that much for one simple reason: rare alleles with small effects don’t account for that much of the variance in trait values. Like if the RDR method’s estimate of heritability is accurate for height, we should expect rare variants to raise the variance explained from 45% to 55%, which would result in a ~10% increase in expected height if you were selecting embryos based on that trait.
That would be nice, but it’s not necessary for embryo selection to work.
If your friend wants to talk about this more I’d be happy to have a conversation with them.