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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 c

by 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.
        ZhuanXia 7y ago
        >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. Bit of a stretch there mate; that doesn't follow at all.
        pcrh 7y ago
        Well... Accounting for 2.5% of the intelligence variation through genetics does lead to the conclusion that 97.5% of high IQ is not accounted for by (known) genetic variation.
    - mlyle 7y ago
      > the enriched population does not help as high IQ is not caused by rare variants. The enriched population tends to have a higher population of these common variants. Saying it "does not help" is kinda silly-- the authors and reviewers behind this Nature MP pub disagree with you, as do I ;) In the end, we have small randomized sample studies directly on IQ; enriched case-controlled studies like this one; and large studies looking at proxy variables (educational attainment). They have all come up with broadly similar estimates for the effects of polygenic variation on general intelligence. That is, we have enough information to be reasonably confident in an upper bound.
      - ZhuanXia 7y ago
        I suppose I should have said it does not help much. You are right; it does help.
- 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.

by pcrh 7y ago

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.
        ZhuanXia 7y ago
        >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. Bit of a stretch there mate; that doesn't follow at all.
        pcrh 7y ago
        Well... Accounting for 2.5% of the intelligence variation through genetics does lead to the conclusion that 97.5% of high IQ is not accounted for by (known) genetic variation.
  - mlyle 7y ago
    > the enriched population does not help as high IQ is not caused by rare variants. The enriched population tends to have a higher population of these common variants. Saying it "does not help" is kinda silly-- the authors and reviewers behind this Nature MP pub disagree with you, as do I ;) In the end, we have small randomized sample studies directly on IQ; enriched case-controlled studies like this one; and large studies looking at proxy variables (educational attainment). They have all come up with broadly similar estimates for the effects of polygenic variation on general intelligence. That is, we have enough information to be reasonably confident in an upper bound.
    - ZhuanXia 7y ago
      I suppose I should have said it does not help much. You are right; it does help.
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.