4 ms·

We don’t need the causal variants for embryo selection, just the predictive variants. We have this for height now. The only reason we don’t have this for IQ now

We don’t need the causal variants for embryo selection, just the predictive variants. We have this for height now. The only reason we don’t have this for IQ now is everyone doing GWAS studies are too chicken to put an IQ test in with their other measures. As the cost of a sequence declines, this will not last. Obviously, this is not an issue if there is state involvement.

deleted 7y ago
[deleted]
pcrh 7y ago
People have done IQ vs genetic variation in GWAS. They find that there is almost no impact of common variants on IQ. Example: >A genome-wide polygenic score constructed from the GWA results accounted for 1.6% of the variance of intelligence in the normal range in an unselected sample of 3414 individuals, which is comparable to the variance explained by GWA studies of intelligence with substantially larger sample sizes. https://www.ncbi.nlm.nih.gov/pubmed/29731509 https://www.ncbi.nlm.nih.gov/pubmed/29731509
- ZhuanXia 7y ago
  Yes. For polygenic traits like IQ we need millions of samples tagged with IQ. 3000 is a really small sample.
  - mlyle 7y ago
    The linked study uses ~1200 very high IQ individuals (4 sigma out), so it has the same population of very high IQ individuals as you'd have in a random sample of tens of millions. There's also been large studies that have used years of educational attainment as a moderately-correlated proxy for IQ.
    - ZhuanXia 7y ago
      the enriched population does not help as high IQ is not caused by rare variants. Rather it is the proportion of common variants that increase IQ to common variants that decrease it. This is why we need millions of samples.
      - pcrh 7y ago
        I think you perhaps misunderstand the study's conclusions (and that of most GWAS on intelligence). They conclude that high IQ (>170) is mostly not caused by genetic variants.
        ZhuanXia 7y ago
        >They conclude that high IQ (>170) is mostly not caused by genetic variants. The abstract does not mention that; they claim: "This study shows the utility of extreme trait selection for genetic study of intelligence and suggests that extremely high intelligence is continuous genetically with normal-range intelligence in the population." I don't think anyone would seriously claim that high IQ is mostly not caused by genetic variants, given the prior knowledge of the heritability of IQ.
        pcrh 7y ago
        The full text is available here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987166/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987166/ In the conclusions section they state: >Focusing on the core 4-test g measure, we think that accounting for 1.6% of the variance of intelligence is exciting for several reasons. First, this effect size is greater than the effect sizes from previous GWA studies of the normal range of intelligence.45 The effect size of 1.6% represents >2.5% of the heritable variance of intelligence, which is comparable to the most robust effect sizes in behavioural research.46 That they are "excited" to account for at best 2.5% of high IQ through genetics suggests that genetics is not a large contributor to high intelligence. Previous studies demonstrating high heritability of IQ did not discriminate between genetic inheritance and social/cultural/environmental inheritance. Clearly, the latter are more significant contributors than is genetics.
  - pcrh 7y ago
    If you need millions, it means that there are no common enough variants with a large effect size.
    - ZhuanXia 7y ago
      Yes. That is true. It will take hundreds of edits to increase IQ several standard deviations. This is not a problem for embryo selection.
- gwern 7y ago
  You are making some serious mistakes in your citation of that: 1. a polygenic score is not 'the impact of common variants'; that's the SNP heritability, such as the GCTA or LDSC. It's not 1.6%, it's closer to 30%. You edited out the part of the abstract which correctly specifies this: "the single-nucleotide polymorphism heritability for the extreme IQ trait was 0.33 (0.02)" 2. that is not the best predictor of intelligence; it is not now (that would be Allegrini et al 2018), and it was not then either - you have to go all the way back to like 2014 for 1.6% to be SOTA and I'm puzzled why you cite Zabaneh at all, which is one of the most obscure IQ GWASes... The actual SOTA is 11% or higher. 3. your claims about power are obviously wrong, as Allegrini et al 2018 uses far less than 'tens of millions' and still greatly outperforms it. (Which has something to do with those rare beneficial variants not existing which they were looking for...) So, we can predict 11%, not 1.6%, and common variants have a large impact, 3x that, and rare variants account for even more, easily 50% including what you might call semi-rare variants (https://www.biorxiv.org/content/10.1101/106203v2 https://www.biorxiv.org/content/10.1101/106203v2).
  - pcrh 7y ago
    Even if you are right 11% is a pretty meagre contribution, when compared to most other biological traits..
    - gwern 7y ago
      No, it's not. You are still confusing heritability with PGS, and that's a much better PGS than is available for most 'biological' traits. Look through something like LD Hub to get an idea of average GWAS PGSes currently: <11% is very common.
corporate_shi11 7y ago
We have already identified variants than can account for over 10% of variation in intelligence. Researchers have gotten around the lack of GWAS IQ test results by using years of educational attainment as a reliable proxy. These results have been achieved in less than 2 years and the science is rapidly progressing. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985927/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985927/
stanfordkid 7y ago
Polygenic scores for IQ are correlated with other traits that are less desirable (schizophrenia for example). I think the lift in IQ you get from embryo selection is counteracted by a lot of other (negative) factors. It is also unclear to what degree epigenetic inheritance plays in IQ. My opinion is the 8-10 IQ point boost is less than variance from unknown factors relating to doing IVF versus natural birth. In other words I would still go with natural birth (which has been time tested by evolution)
- ZhuanXia 7y ago
  >Polygenic scores for IQ are correlated with other traits that are less desirable (schizophrenia for example). Nope. IQ is negatively correlated with most mental illness. It is certainly not positively correlated with schizophrenia: https://www.gwern.net/iq https://www.gwern.net/iq
  - mlyle 7y ago
    This has positively nothing to do with what he said.
    - ZhuanXia 7y ago
      Read it again. It clearly does.
      - mlyle 7y ago
        I read it again, it clearly doesn't. ;) As it turns out, we have multiple contradictory findings about whether high IQ is positively or negatively correlated with mental illness. But even if you believe there's a negative correlation, it doesn't mean that many predictive SNPs can't predict both. E.g. cloud cover is predictive both for rainfall and heavy snow. However, heavy snow is negatively correlated with rainfall. The latter doesn't negate the former.
  - stanfordkid 7y ago
    This is certainly not something that can be answered with a simple Yes or No. I am by no means saying that the underlying traits are casually related — only that metrics which predict one may also predict the other. The human brain is a complex system and IQ itself is a very simplistic way to characterize it. Think of it this way: imagine IQ is like electricity powering a city. Different city configurations have very different power and load requirements. You might find that, in general, cities with more power function better. But perhaps the well functioning cities also had better transmission infrastructure. If you applied the rule of “more power is better” to a city without that infrastructure it would blow fuses everywhere and cause chaos. With this example aside, In fact the science does say that there is a relationship: https://www.nature.com/articles/s41380-018-0332-x?WT.feed_name=subjects_neuroscience https://www.nature.com/articles/s41380-018-0332-x?WT.feed_na...
frgtpsswrdlame 7y ago
There are plenty of GWASs on IQ, they just struggle to replicate each other.
buboard 7y ago
He targeted CCR5 which does have some (pretty striking) effect in mouse learning and synaptic turnover in particular. He was aware of that study. https://elifesciences.org/articles/20985 https://elifesciences.org/articles/20985

deleted 7y ago

[deleted]

pcrh 7y ago

People have done IQ vs genetic variation in GWAS. They find that there is almost no impact of common variants on IQ. Example: >A genome-wide polygenic score constructed from the GWA results accounted for 1.6% of the variance of intelligence in the normal range in an unselected sample of 3414 individuals, which is comparable to the variance explained by GWA studies of intelligence with substantially larger sample sizes. https://www.ncbi.nlm.nih.gov/pubmed/29731509 https://www.ncbi.nlm.nih.gov/pubmed/29731509

ZhuanXia 7y ago
Yes. For polygenic traits like IQ we need millions of samples tagged with IQ. 3000 is a really small sample.
- mlyle 7y ago
  The linked study uses ~1200 very high IQ individuals (4 sigma out), so it has the same population of very high IQ individuals as you'd have in a random sample of tens of millions. There's also been large studies that have used years of educational attainment as a moderately-correlated proxy for IQ.
  - ZhuanXia 7y ago
    the enriched population does not help as high IQ is not caused by rare variants. Rather it is the proportion of common variants that increase IQ to common variants that decrease it. This is why we need millions of samples.
    - pcrh 7y ago
      I think you perhaps misunderstand the study's conclusions (and that of most GWAS on intelligence). They conclude that high IQ (>170) is mostly not caused by genetic variants.
      - ZhuanXia 7y ago
        >They conclude that high IQ (>170) is mostly not caused by genetic variants. The abstract does not mention that; they claim: "This study shows the utility of extreme trait selection for genetic study of intelligence and suggests that extremely high intelligence is continuous genetically with normal-range intelligence in the population." I don't think anyone would seriously claim that high IQ is mostly not caused by genetic variants, given the prior knowledge of the heritability of IQ.
        pcrh 7y ago
        The full text is available here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987166/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987166/ In the conclusions section they state: >Focusing on the core 4-test g measure, we think that accounting for 1.6% of the variance of intelligence is exciting for several reasons. First, this effect size is greater than the effect sizes from previous GWA studies of the normal range of intelligence.45 The effect size of 1.6% represents >2.5% of the heritable variance of intelligence, which is comparable to the most robust effect sizes in behavioural research.46 That they are "excited" to account for at best 2.5% of high IQ through genetics suggests that genetics is not a large contributor to high intelligence. Previous studies demonstrating high heritability of IQ did not discriminate between genetic inheritance and social/cultural/environmental inheritance. Clearly, the latter are more significant contributors than is genetics.
- pcrh 7y ago
  If you need millions, it means that there are no common enough variants with a large effect size.
  - ZhuanXia 7y ago
    Yes. That is true. It will take hundreds of edits to increase IQ several standard deviations. This is not a problem for embryo selection.
gwern 7y ago
You are making some serious mistakes in your citation of that: 1. a polygenic score is not 'the impact of common variants'; that's the SNP heritability, such as the GCTA or LDSC. It's not 1.6%, it's closer to 30%. You edited out the part of the abstract which correctly specifies this: "the single-nucleotide polymorphism heritability for the extreme IQ trait was 0.33 (0.02)" 2. that is not the best predictor of intelligence; it is not now (that would be Allegrini et al 2018), and it was not then either - you have to go all the way back to like 2014 for 1.6% to be SOTA and I'm puzzled why you cite Zabaneh at all, which is one of the most obscure IQ GWASes... The actual SOTA is 11% or higher. 3. your claims about power are obviously wrong, as Allegrini et al 2018 uses far less than 'tens of millions' and still greatly outperforms it. (Which has something to do with those rare beneficial variants not existing which they were looking for...) So, we can predict 11%, not 1.6%, and common variants have a large impact, 3x that, and rare variants account for even more, easily 50% including what you might call semi-rare variants (https://www.biorxiv.org/content/10.1101/106203v2 https://www.biorxiv.org/content/10.1101/106203v2).
- pcrh 7y ago
  Even if you are right 11% is a pretty meagre contribution, when compared to most other biological traits..
  - gwern 7y ago
    No, it's not. You are still confusing heritability with PGS, and that's a much better PGS than is available for most 'biological' traits. Look through something like LD Hub to get an idea of average GWAS PGSes currently: <11% is very common.

corporate_shi11 7y ago

We have already identified variants than can account for over 10% of variation in intelligence. Researchers have gotten around the lack of GWAS IQ test results by using years of educational attainment as a reliable proxy. These results have been achieved in less than 2 years and the science is rapidly progressing. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985927/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985927/

stanfordkid 7y ago

Polygenic scores for IQ are correlated with other traits that are less desirable (schizophrenia for example). I think the lift in IQ you get from embryo selection is counteracted by a lot of other (negative) factors. It is also unclear to what degree epigenetic inheritance plays in IQ. My opinion is the 8-10 IQ point boost is less than variance from unknown factors relating to doing IVF versus natural birth. In other words I would still go with natural birth (which has been time tested by evolution)

ZhuanXia 7y ago
>Polygenic scores for IQ are correlated with other traits that are less desirable (schizophrenia for example). Nope. IQ is negatively correlated with most mental illness. It is certainly not positively correlated with schizophrenia: https://www.gwern.net/iq https://www.gwern.net/iq
- mlyle 7y ago
  This has positively nothing to do with what he said.
  - ZhuanXia 7y ago
    Read it again. It clearly does.
    - mlyle 7y ago
      I read it again, it clearly doesn't. ;) As it turns out, we have multiple contradictory findings about whether high IQ is positively or negatively correlated with mental illness. But even if you believe there's a negative correlation, it doesn't mean that many predictive SNPs can't predict both. E.g. cloud cover is predictive both for rainfall and heavy snow. However, heavy snow is negatively correlated with rainfall. The latter doesn't negate the former.
- stanfordkid 7y ago
  This is certainly not something that can be answered with a simple Yes or No. I am by no means saying that the underlying traits are casually related — only that metrics which predict one may also predict the other. The human brain is a complex system and IQ itself is a very simplistic way to characterize it. Think of it this way: imagine IQ is like electricity powering a city. Different city configurations have very different power and load requirements. You might find that, in general, cities with more power function better. But perhaps the well functioning cities also had better transmission infrastructure. If you applied the rule of “more power is better” to a city without that infrastructure it would blow fuses everywhere and cause chaos. With this example aside, In fact the science does say that there is a relationship: https://www.nature.com/articles/s41380-018-0332-x?WT.feed_name=subjects_neuroscience https://www.nature.com/articles/s41380-018-0332-x?WT.feed_na...

frgtpsswrdlame 7y ago

There are plenty of GWASs on IQ, they just struggle to replicate each other.

buboard 7y ago

He targeted CCR5 which does have some (pretty striking) effect in mouse learning and synaptic turnover in particular. He was aware of that study. https://elifesciences.org/articles/20985 https://elifesciences.org/articles/20985