9 ms·

Gene discovery from a genome-wide association study of educational attainment

70 points by gwern 8y ago

gwern 8y ago
Media: https://www.theatlantic.com/science/archive/2018/07/staying-in-school-genetics/565832/ https://www.theatlantic.com/science/archive/2018/07/staying-... FAQ: https://www.thessgac.org/faqs https://www.thessgac.org/faqs
frgtpsswrdlame 8y ago
I'll have to read this later since I'm at work but is there a layman's explanation for how these studies distinguish environmental and genetic influence? I don't see how you could accurately separate the two.
- AstralStorm 8y ago
  You don't in this phase, since both feed back into another. After high correlates are found, further experiments will disentangle the relationship.
- gwern 8y ago
  Not entirely sure what you mean: genes cause environments, and interact with environments. If you mean something like whether it's just picking up ancestry markers for families which happen to be rich etc, there are a lot of methodological components which try to minimize the more obvious ways of population stratification affecting results. The most iron-clad part of showing direct gene->trait causation is the 4 sibling-comparison studies, where you see whether you can predict the difference between 2 siblings; as they have identical ancestries, families, locations etc, their environments are near-identical in the first place, and since meiosis at conception randomizes genes between siblings, success in sibling comparison shows the genes must be causal. IQ GWASes have always passed the within-family test since Rietveld et al 2013, and this is no exception.
  - nabla9 8y ago
    > The most iron-clad part of showing direct gene->trait causation is the 4 I would not say it's iron-clad gene->trait causation. Even wth 4 sibling-comparisons and the same environmental factors, it can be gene-environment interaction -> trait Their study finds that genes associated with attainment are active in neurons. These genes might just protect brain from environmental damage. For example: from malnutrition by using nutrients more effectively, infections, heavy metals, or mother smoking or using alcohol, ...
  - frgtpsswrdlame 8y ago
    >If you mean something like whether it's just picking up ancestry markers for families which happen to be rich etc, there are a lot of methodological components which try to minimize the more obvious ways of population stratification affecting results. Yeah this is actually what I'm interested in. >The most iron-clad part of showing direct gene->trait causation is the 4 sibling-comparison studies, where you see whether you can predict the difference between 2 siblings; as they have identical ancestries, families, locations etc, their environments are near-identical in the first place, and since meiosis at conception randomizes genes between siblings, success in sibling comparison shows the genes must be causal. IQ GWASes have always passed the within-family test since Rietveld et al 2013, and this is no exception. Couldn't this still lead to an overstating of the effect? So two brothers John and Jim have different builds due to genetics, John is a bit shorter and stockier and Jim is a bit taller and leaner. When they play with each other as children John usually wins when they wrestle and Jim usually wins when they play basketball. They both like winning so in highschool John joins the wrestling team and Jim joins the basketball team. Now if I do some gene testing wizardry on them as adults and try to determine the difference in basketball-skill I'll predict a large gap due to height genes and I'll get one. But part of that skill gap is due to environment (4 years of basketball practice) yet still getting attributed to genes.
    - gwern 8y ago
      > ...When they play with each other as children John usually wins when they wrestle and Jim usually wins when they play basketball... No, this is still genetic causation (and something like this story is usually what is invoked for why the heritability of intelligence increases with age: more intelligent people seeking out niches which then encourage intelligence further rather than preferring to veg out in front of the boobtube, leading shared-environment to disappear while the permanent ongoing influence from genetics leads to heritability increases). What's the definition of causation? It's a 'difference which makes a difference', or in Pearlean terms, if you reach in and do surgery on one node in a causal network, the counterfactual difference. So in your basketball example, what if we reached in with CRISPR, say, and edited just the genes for builds in John to make him taller/leaner? What is the counterfactual of our intervention on the node of genes? As he grows up and becomes taller/leaner, now he still likes winning and playing with his brother is an even challenge, so he joins the basketball team along with Jim and they do well and keep playing and so on and so forth and your basketball PGS predicts less or no difference between them (since we caused them to have the same relevant genes) and indeed there is less or no difference; and if we had instead edited the other way, it'd go the other way etc. Thus, causation. That the causal pathway of the genes goes 'outside the skin', as some people put it, makes no difference that makes a difference for this particular question. (A similar point applies to the 'nature of nurture' findings mentioned in Lee et al 2018 and the two earlier papers. Are they genetic causation? Yes, because if you counterfactually changed the genes and nothing but the genes, you would get different outcomes. They are differences which make a difference. They are, however, causal on things you didn't expect - eg edits in children would cause gains in grandchildren rather than the children.)
- rossdavidh 8y ago
  Relevant, from the article FAQ: "A recent study of Icelandic families showed that the parental allele that is not passed on to the parent’s offspring is still associated with the child’s educational attainment, suggesting that GWAS results for educational attainment partly represent these intergenerational pathways (Kong et al. 2018). Our sibling analyses yield results that are consistent with this conclusion (see FAQ 2.4)." So, it might just be both environment and the genetic influence both correlating to the same thing, and they admit as much.
- polski-g 8y ago
  You do a twin study comparing monozgyotic to dizygotic twin pairs. The variance of the trait between the two pairs is the genetic effect. Determining environment effect is done by doing twin-reared-apart studies (to separate shared vs non-shared environment).
cryoshon 8y ago
taking all of the associations into account and making a polygenic predictor score "does a lousy job predicting the outcome for any specific individual, but it can explain 11 percent of the population-wide variation in years of schooling." only 11 percent. this tells us that the remainder is more likely to be attributable to environmental factors. in other words, even with a view of the genes, we would need to encourage education more strenuously if we wanted to improve educational outcomes for society.
- deugtniet 8y ago
  Full disclosure: I have attended multiple presentation on this paper by some of these authors, and I'm doing a PhD in quantitative Genetics. So I like to think I have something to add. But I'm not an expert on educational attainment, so correct me if I'm wrong. The 11% of variance that can be predicted using the current information of a fairly bad genetic predictor. The predictor is bad because many cohorts used in this study do not share all their information, but only share so called summary statistics. Which are combined into a prediction model. If all the individual level data is available, it becomes possible to get a much better prediction model. In addition there are ways to estimate how much can be predicted from genetic information, a term called heritability. Heritability can be estimated from so called twin studies. Where twins who are genetically identical (monozygotic) are compared to twins who are not genetically identical (dizygotic). In this way you can measure the environmental effect (the variation seen in the monozygotic twins) and the genetic effect (the variation that is seen in the dizygotic twins compared to the monozygotic twins). This is, of course, a gross oversimplification, but can provide reasonable measures of an upper bound of what can be explained genetically For most traits this upper bound is around 0.5 R^2, and I believe for educational attainment a bit higher, but I could not find it in the paper or a quick google search. Another factor in this case is that there are unmeasured genotypes which can explain some extra variation. There are also solutions for this. Which are able to explain the upper bound of what can be predicted from the data at hand. For instance meaning that you can find 80% of all the genetic variation using the genetic measurements that you have. But you often need individual level data for this. Something which cohorts are not often prepared to share. Another complicating factor is the heterogeneous nature of the phenotype: educational attainment is different per country. So it's hard to say what's really being measured. It's likely very different in France, compared to say The Netherlands. Due to the differing nature of their educational systems. Personally I'm morally conflicted by these studies which measure intelligence. It's very interesting to see the practical outcomes from the paper. I've seen an example where it's well powered to stratify high educational attainment and low educational attainment individuals for social science studies. But I'm of the opinion that this may be a slippery slope towards misinterpretation, as we currently see in the whole IQ business. As well as too strong an emphasis on being 'smart' in certain social groups. We know Intelligence (or whatever is being measured) is heritable. But I'm not fond of the implications which people attach to these studies. Even though I know people are going to act on it. For the earliest examples of this, I'm going to look at certain east Asian countries where ethics may be very different compared to the western views.
yk 8y ago
From the discussion: > However, theoretical projections that failed to consider heterogeneity of effect sizes were optimistic Our and others’ findings suggest that imperfect genetic correlation across cohorts will be the norm for phenotypes, such as educational attainment, that are environmentally contingent. So it is somewhat worrying that genetics predict the clearly environmentally contingent like educational attainment better than "cognitive performance." > Our results also highlight two caveats to the use of the polygenic scores in research. First, our within-family analyses suggest that GWAS estimates may overstate the causal effect sizes: if educational attainment-increasing genotypes are associated with parental educational attainment-increasing genotypes, which are in turn associated with rearing environments that promote educational attainment, then failure to control for rearing environment will bias GWAS estimates. That is a very complicated way of saying that some genes express themselves by black skin, and these genes have a strong effect on funds available to the school.
- gwern 8y ago
  > So it is somewhat worrying that genetics predict the clearly environmentally contingent like educational attainment better than "cognitive performance." I don't agree that schools are any more 'clearly environmentally contingent' than intelligence, especially with the mandatory public schooling applicable to all of the cohorts used. > That is a very complicated way of saying that some genes express themselves by black skin That's a remarkable assertion, considering that this dataset is made of 100% white people, works on white siblings like Swedish twins, and the PGS is still predictive when applied within a separate African-American dataset.
  - yk 8y ago
    > I don't agree that schools are any more 'clearly environmentally contingent' than intelligence, Clearly I can change all the rules governing schools without changing the genetics of any of the students. So you are claiming that it is possible that if intelligence could be as environmentally contingent like school system, then one would need to show that this type of study can produce interesting results in the first place. > That's a remarkable assertion, I read the sentence as a general qualifier for this kind of studies. But the objection is, that these genes would produce a clear signal in this kind of studies without any of the causality taking place inside of a brain. (And unlike 'intelligence,' I can actually define what I mean by 'black skin' 'school funding' and 'average neighborhood income.' ) So for the study to have any kind of explainative effect, it needs to show that the effect is created by anything that can be reasonably called intelligence, instead of something that takes place completely outside of the brain.
deleted 8y ago
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haberman 8y ago
I absolutely love that this study was accompanied by a FAQ (https://www.thessgac.org/faqs https://www.thessgac.org/faqs). My interpretation of this FAQ is that it provides a great deal of context that would be apparent to people in the field (and therefore not included in the paper itself) but is critical background for anyone else who is trying to make sense of it. It therefore provides a bridge between the highly technical paper itself and journalism which too often misunderstands the true meaning of research results. I think this is so valuable. I hope that this kind of thing will catch on for more research that attracts public interest.
- 21 8y ago
  I think the FAQ has a strong self-defence purpose. See the last question covered, which is probably the first one people care about: > 3.7. Could this kind of research lead to discrimination against, or stigmatization of, people with the relevant genetic variants? If so, why conduct this research?
- dekhn 8y ago
  I read the entire FAQ. It's gold. Every major paper that makes strong claims should be required to write as much explaining. For example, after reading the FAQ, I understand now that most GWAS papers overstate everything about their findings. The FAQ is much more measured and explicates the severe restrictions on interpreting the findings.
rfinney 8y ago
The 207 page Supplementary Material is here: https://static-content.springer.com/esm/art%3A10.1038%2Fs41588-018-0147-3/MediaObjects/41588_2018_147_MOESM1_ESM.pdf https://static-content.springer.com/esm/art%3A10.1038%2Fs415... (probably pay walled). Interesting discussion of genes and pathways involved around page 84. "Results: Causal Genes and Enriched Gene Sets" I'll just type in the pathways. ( Supplementary Figure 22.) "Brain Specific Expression of Significantly Enriched Gene Sets across Development. (page 196)": Chromatic modification, protein binding transcription factor activity, npBAF complex, Central nervous system neuron differentiation, forebrain development, partial posttnatal lethality, abnormal cerebral cortext morphology, endometrial cancer , GAB1 signalosome, regulation of nervous system development, telencephaol cell migration, protein tyrosine kinase activity , neuron recognition, axon guidance, small cerebellum protein phosphatase regulator activity, signaling by eGFR, dendrite morphogenesis, signaling by NGF, regulation of neuron projection development, behavioral fear response, DAG and IP signaling, associative learning , voltage-gate calcium channel activity , ataxia, extracellular-glutamte-gate ion channel activity, post NMDA receptor activation events, regulation of neurotransmitter levels, regulation of synaptic transmission, synapse part ,gate channel activity. Single Nucleotide Polymorphisms (snps) discussed in supplement are:rs10189857 rs1167898 rs11678980 rs18235539 rs182355396 rs186456786 rs186456786 rs186456786 rs5951458 rs61734410 Links to dbsnp for snps discussed in supplement: https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=10189857 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=101... https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=1167898 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=116... https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=11678980 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=116... https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=18235539 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=182... https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=182355396 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=182... https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=186456786 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=186... https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=5951458 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=595... https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=61734410 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=617... https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=62422687 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=624...
- deleted 8y ago
deleted 8y ago
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oldgradstudent 8y ago
In what sense is this a "discovery"? Observational studies of this type cannot show causality, and the results have not been confirmed by independent methods.
- gwern 8y ago
  > Observational studies of this type cannot show causality They can: sibling comparisons. > the results have not been confirmed by independent methods. They're tested out of sample many times (4 for sibling comparisons alone!), and you can find many other papers successfully using the IQ GWASes. Belsky et al 2018 just came out a few weeks ago, for a particularly good example testing OP's PGS. (The PGS has been out since like March, so several papers have used it.)
  - oldgradstudent 8y ago
    >> Observational studies of this type cannot show causality >They can: sibling comparisons. But then they get much lower concordance so they come up with various ad-hoc hypotheses to explain it, instead of acknowledging the negative result. This is an hypothesis generating paper, using a highly suspect methods. Not a discovery.
pwdisswordfish2 8y ago
> “If you did a study like ours 100 years ago, the strongest genetic predictor of education would be how many X chromosomes you had, because society was set up in a way that it was much harder for women to get educated than men,” says Benjamin. Likewise, many of the genes that are associated with education today are likely important “because of how today’s educational system is set up. It requires people to sit at desks for hours, and listen to instructions from a teacher. People who get restless, or are less obedient to authority, will fare less well in that environment.” I think the above snip (ha) from https://www.theatlantic.com/science/archive/2018/07/staying-in-school-genetics/565832/ https://www.theatlantic.com/science/archive/2018/07/staying-... is useful in interpreting the results.
- wycs 8y ago
  I would much prefer direct IQ correlates rather than using education as a proxy for something better measured with IQ tests.
  - projectramo 8y ago
    What is “better measured” with IQ tests?
    - laretluval 8y ago
      Intelligence.
      - projectramo 8y ago
        I see so much work before me. Just google it: https://futurism.com/intelligence-changing-what-you-think-you-know-part-one/ https://futurism.com/intelligence-changing-what-you-think-yo...
        frgtpsswrdlame 8y ago
        Do you have more good info on the subject?
peregrine 8y ago
Has anyone made a tool to run your own 23andme genome data through this and get a score yet?
- deleted 8y ago
  [deleted]
- jjtheblunt 8y ago
  check out promethease.com
xenadu02 8y ago
From the FAQ: > The current study further confirmed the finding from our earlier work that the effects of individual genetic variants on educational attainment are extremely small. The average effect size across the 1,271 genetic variants was just 1.8 weeks of schooling per allele; even the SNPs with the strongest associations only predicted around 3 weeks of additional schooling per allele. Taken together, these 1,271 SNPs accounted for just 3.9% of the variation across individuals in years of education completed. > Here is another way to think about this result. Imagine that we used the results for these 1,271 genetic variants (not the ~1 million SNPs across entire genome we discuss in FAQ 2.3) to predict the educational attainment for a new group of people (separate from our discovery sample). We could then compare each individual’s predicted educational attainment to their actual educational attainment. If we did so, our results suggest that we would find that the predictions and actual outcomes correlate only very modestly (at about r = 0.20). That, in turn, means that if someone were predicted to complete an above average number of years of schooling (i.e., to be in the top half of educational attainment), that person would have about a 58% chance of actually being in the top half of educational attainment. Fifty-eight percent is better than chance (i.e., 50%), suggesting that a prediction based on these 1,271 SNPs has more power to predict educational attainment than a coin flip—but only a bit more power. By contrast, a prediction based on a polygenic score that combines ~1 million SNPs that we studied (see FAQs 1.5 & 2.3) has more predictive power: r = 0.33, corresponding to 11% of the variation across individuals. > The contrast between the 3.9% of the variation predicted by the 1,271 SNPs and the 20% known to be explained by common SNPs (see FAQ 1.7) implies that there are many other SNPs that have not yet been identified. Even larger sample sizes will be needed to identify them. They only included people of European ancestry to eliminate sources of noise and cofounding factors. The effect size is very small, yet it does exist. This seems to prove that intelligence influenced by genetics but is affected by many thousands of genetic variations. There is no "smart" gene, just lots and lots of randomness.
- notduncansmith 8y ago
  This makes sense. People use different combinations of skills and physical traits to excel in arts, sports, and business. It seems natural then that “intelligence” would encompass a wide range of abilities and traits.
zavi 8y ago
Please don't post Dropbox links, the PDF downloads are unusable on Android.
- jjtheblunt 8y ago
  Android is confused by PDFs ?

70 points by gwern 8y ago

Media: https://www.theatlantic.com/science/archive/2018/07/staying-in-school-genetics/565832/ https://www.theatlantic.com/science/archive/2018/07/staying-... FAQ: https://www.thessgac.org/faqs https://www.thessgac.org/faqs

frgtpsswrdlame 8y ago

I'll have to read this later since I'm at work but is there a layman's explanation for how these studies distinguish environmental and genetic influence? I don't see how you could accurately separate the two.

AstralStorm 8y ago
You don't in this phase, since both feed back into another. After high correlates are found, further experiments will disentangle the relationship.
gwern 8y ago
Not entirely sure what you mean: genes cause environments, and interact with environments. If you mean something like whether it's just picking up ancestry markers for families which happen to be rich etc, there are a lot of methodological components which try to minimize the more obvious ways of population stratification affecting results. The most iron-clad part of showing direct gene->trait causation is the 4 sibling-comparison studies, where you see whether you can predict the difference between 2 siblings; as they have identical ancestries, families, locations etc, their environments are near-identical in the first place, and since meiosis at conception randomizes genes between siblings, success in sibling comparison shows the genes must be causal. IQ GWASes have always passed the within-family test since Rietveld et al 2013, and this is no exception.
- nabla9 8y ago
  > The most iron-clad part of showing direct gene->trait causation is the 4 I would not say it's iron-clad gene->trait causation. Even wth 4 sibling-comparisons and the same environmental factors, it can be gene-environment interaction -> trait Their study finds that genes associated with attainment are active in neurons. These genes might just protect brain from environmental damage. For example: from malnutrition by using nutrients more effectively, infections, heavy metals, or mother smoking or using alcohol, ...
- frgtpsswrdlame 8y ago
  >If you mean something like whether it's just picking up ancestry markers for families which happen to be rich etc, there are a lot of methodological components which try to minimize the more obvious ways of population stratification affecting results. Yeah this is actually what I'm interested in. >The most iron-clad part of showing direct gene->trait causation is the 4 sibling-comparison studies, where you see whether you can predict the difference between 2 siblings; as they have identical ancestries, families, locations etc, their environments are near-identical in the first place, and since meiosis at conception randomizes genes between siblings, success in sibling comparison shows the genes must be causal. IQ GWASes have always passed the within-family test since Rietveld et al 2013, and this is no exception. Couldn't this still lead to an overstating of the effect? So two brothers John and Jim have different builds due to genetics, John is a bit shorter and stockier and Jim is a bit taller and leaner. When they play with each other as children John usually wins when they wrestle and Jim usually wins when they play basketball. They both like winning so in highschool John joins the wrestling team and Jim joins the basketball team. Now if I do some gene testing wizardry on them as adults and try to determine the difference in basketball-skill I'll predict a large gap due to height genes and I'll get one. But part of that skill gap is due to environment (4 years of basketball practice) yet still getting attributed to genes.
  - gwern 8y ago
    > ...When they play with each other as children John usually wins when they wrestle and Jim usually wins when they play basketball... No, this is still genetic causation (and something like this story is usually what is invoked for why the heritability of intelligence increases with age: more intelligent people seeking out niches which then encourage intelligence further rather than preferring to veg out in front of the boobtube, leading shared-environment to disappear while the permanent ongoing influence from genetics leads to heritability increases). What's the definition of causation? It's a 'difference which makes a difference', or in Pearlean terms, if you reach in and do surgery on one node in a causal network, the counterfactual difference. So in your basketball example, what if we reached in with CRISPR, say, and edited just the genes for builds in John to make him taller/leaner? What is the counterfactual of our intervention on the node of genes? As he grows up and becomes taller/leaner, now he still likes winning and playing with his brother is an even challenge, so he joins the basketball team along with Jim and they do well and keep playing and so on and so forth and your basketball PGS predicts less or no difference between them (since we caused them to have the same relevant genes) and indeed there is less or no difference; and if we had instead edited the other way, it'd go the other way etc. Thus, causation. That the causal pathway of the genes goes 'outside the skin', as some people put it, makes no difference that makes a difference for this particular question. (A similar point applies to the 'nature of nurture' findings mentioned in Lee et al 2018 and the two earlier papers. Are they genetic causation? Yes, because if you counterfactually changed the genes and nothing but the genes, you would get different outcomes. They are differences which make a difference. They are, however, causal on things you didn't expect - eg edits in children would cause gains in grandchildren rather than the children.)
rossdavidh 8y ago
Relevant, from the article FAQ: "A recent study of Icelandic families showed that the parental allele that is not passed on to the parent’s offspring is still associated with the child’s educational attainment, suggesting that GWAS results for educational attainment partly represent these intergenerational pathways (Kong et al. 2018). Our sibling analyses yield results that are consistent with this conclusion (see FAQ 2.4)." So, it might just be both environment and the genetic influence both correlating to the same thing, and they admit as much.
polski-g 8y ago
You do a twin study comparing monozgyotic to dizygotic twin pairs. The variance of the trait between the two pairs is the genetic effect. Determining environment effect is done by doing twin-reared-apart studies (to separate shared vs non-shared environment).

cryoshon 8y ago

taking all of the associations into account and making a polygenic predictor score "does a lousy job predicting the outcome for any specific individual, but it can explain 11 percent of the population-wide variation in years of schooling." only 11 percent. this tells us that the remainder is more likely to be attributable to environmental factors. in other words, even with a view of the genes, we would need to encourage education more strenuously if we wanted to improve educational outcomes for society.

deugtniet 8y ago
Full disclosure: I have attended multiple presentation on this paper by some of these authors, and I'm doing a PhD in quantitative Genetics. So I like to think I have something to add. But I'm not an expert on educational attainment, so correct me if I'm wrong. The 11% of variance that can be predicted using the current information of a fairly bad genetic predictor. The predictor is bad because many cohorts used in this study do not share all their information, but only share so called summary statistics. Which are combined into a prediction model. If all the individual level data is available, it becomes possible to get a much better prediction model. In addition there are ways to estimate how much can be predicted from genetic information, a term called heritability. Heritability can be estimated from so called twin studies. Where twins who are genetically identical (monozygotic) are compared to twins who are not genetically identical (dizygotic). In this way you can measure the environmental effect (the variation seen in the monozygotic twins) and the genetic effect (the variation that is seen in the dizygotic twins compared to the monozygotic twins). This is, of course, a gross oversimplification, but can provide reasonable measures of an upper bound of what can be explained genetically For most traits this upper bound is around 0.5 R^2, and I believe for educational attainment a bit higher, but I could not find it in the paper or a quick google search. Another factor in this case is that there are unmeasured genotypes which can explain some extra variation. There are also solutions for this. Which are able to explain the upper bound of what can be predicted from the data at hand. For instance meaning that you can find 80% of all the genetic variation using the genetic measurements that you have. But you often need individual level data for this. Something which cohorts are not often prepared to share. Another complicating factor is the heterogeneous nature of the phenotype: educational attainment is different per country. So it's hard to say what's really being measured. It's likely very different in France, compared to say The Netherlands. Due to the differing nature of their educational systems. Personally I'm morally conflicted by these studies which measure intelligence. It's very interesting to see the practical outcomes from the paper. I've seen an example where it's well powered to stratify high educational attainment and low educational attainment individuals for social science studies. But I'm of the opinion that this may be a slippery slope towards misinterpretation, as we currently see in the whole IQ business. As well as too strong an emphasis on being 'smart' in certain social groups. We know Intelligence (or whatever is being measured) is heritable. But I'm not fond of the implications which people attach to these studies. Even though I know people are going to act on it. For the earliest examples of this, I'm going to look at certain east Asian countries where ethics may be very different compared to the western views.

yk 8y ago

From the discussion: > However, theoretical projections that failed to consider heterogeneity of effect sizes were optimistic Our and others’ findings suggest that imperfect genetic correlation across cohorts will be the norm for phenotypes, such as educational attainment, that are environmentally contingent. So it is somewhat worrying that genetics predict the clearly environmentally contingent like educational attainment better than "cognitive performance." > Our results also highlight two caveats to the use of the polygenic scores in research. First, our within-family analyses suggest that GWAS estimates may overstate the causal effect sizes: if educational attainment-increasing genotypes are associated with parental educational attainment-increasing genotypes, which are in turn associated with rearing environments that promote educational attainment, then failure to control for rearing environment will bias GWAS estimates. That is a very complicated way of saying that some genes express themselves by black skin, and these genes have a strong effect on funds available to the school.

gwern 8y ago
> So it is somewhat worrying that genetics predict the clearly environmentally contingent like educational attainment better than "cognitive performance." I don't agree that schools are any more 'clearly environmentally contingent' than intelligence, especially with the mandatory public schooling applicable to all of the cohorts used. > That is a very complicated way of saying that some genes express themselves by black skin That's a remarkable assertion, considering that this dataset is made of 100% white people, works on white siblings like Swedish twins, and the PGS is still predictive when applied within a separate African-American dataset.
- yk 8y ago
  > I don't agree that schools are any more 'clearly environmentally contingent' than intelligence, Clearly I can change all the rules governing schools without changing the genetics of any of the students. So you are claiming that it is possible that if intelligence could be as environmentally contingent like school system, then one would need to show that this type of study can produce interesting results in the first place. > That's a remarkable assertion, I read the sentence as a general qualifier for this kind of studies. But the objection is, that these genes would produce a clear signal in this kind of studies without any of the causality taking place inside of a brain. (And unlike 'intelligence,' I can actually define what I mean by 'black skin' 'school funding' and 'average neighborhood income.' ) So for the study to have any kind of explainative effect, it needs to show that the effect is created by anything that can be reasonably called intelligence, instead of something that takes place completely outside of the brain.

deleted 8y ago

[deleted]

haberman 8y ago

I absolutely love that this study was accompanied by a FAQ (https://www.thessgac.org/faqs https://www.thessgac.org/faqs). My interpretation of this FAQ is that it provides a great deal of context that would be apparent to people in the field (and therefore not included in the paper itself) but is critical background for anyone else who is trying to make sense of it. It therefore provides a bridge between the highly technical paper itself and journalism which too often misunderstands the true meaning of research results. I think this is so valuable. I hope that this kind of thing will catch on for more research that attracts public interest.

21 8y ago
I think the FAQ has a strong self-defence purpose. See the last question covered, which is probably the first one people care about: > 3.7. Could this kind of research lead to discrimination against, or stigmatization of, people with the relevant genetic variants? If so, why conduct this research?
dekhn 8y ago
I read the entire FAQ. It's gold. Every major paper that makes strong claims should be required to write as much explaining. For example, after reading the FAQ, I understand now that most GWAS papers overstate everything about their findings. The FAQ is much more measured and explicates the severe restrictions on interpreting the findings.

rfinney 8y ago

The 207 page Supplementary Material is here: https://static-content.springer.com/esm/art%3A10.1038%2Fs41588-018-0147-3/MediaObjects/41588_2018_147_MOESM1_ESM.pdf https://static-content.springer.com/esm/art%3A10.1038%2Fs415... (probably pay walled). Interesting discussion of genes and pathways involved around page 84. "Results: Causal Genes and Enriched Gene Sets" I'll just type in the pathways. ( Supplementary Figure 22.) "Brain Specific Expression of Significantly Enriched Gene Sets across Development. (page 196)": Chromatic modification, protein binding transcription factor activity, npBAF complex, Central nervous system neuron differentiation, forebrain development, partial posttnatal lethality, abnormal cerebral cortext morphology, endometrial cancer , GAB1 signalosome, regulation of nervous system development, telencephaol cell migration, protein tyrosine kinase activity , neuron recognition, axon guidance, small cerebellum protein phosphatase regulator activity, signaling by eGFR, dendrite morphogenesis, signaling by NGF, regulation of neuron projection development, behavioral fear response, DAG and IP signaling, associative learning , voltage-gate calcium channel activity , ataxia, extracellular-glutamte-gate ion channel activity, post NMDA receptor activation events, regulation of neurotransmitter levels, regulation of synaptic transmission, synapse part ,gate channel activity. Single Nucleotide Polymorphisms (snps) discussed in supplement are:rs10189857 rs1167898 rs11678980 rs18235539 rs182355396 rs186456786 rs186456786 rs186456786 rs5951458 rs61734410 Links to dbsnp for snps discussed in supplement: https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=10189857 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=101... https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=1167898 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=116... https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=11678980 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=116... https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=18235539 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=182... https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=182355396 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=182... https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=186456786 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=186... https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=5951458 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=595... https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=61734410 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=617... https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=62422687 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=624...

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oldgradstudent 8y ago

In what sense is this a "discovery"? Observational studies of this type cannot show causality, and the results have not been confirmed by independent methods.

gwern 8y ago
> Observational studies of this type cannot show causality They can: sibling comparisons. > the results have not been confirmed by independent methods. They're tested out of sample many times (4 for sibling comparisons alone!), and you can find many other papers successfully using the IQ GWASes. Belsky et al 2018 just came out a few weeks ago, for a particularly good example testing OP's PGS. (The PGS has been out since like March, so several papers have used it.)
- oldgradstudent 8y ago
  >> Observational studies of this type cannot show causality >They can: sibling comparisons. But then they get much lower concordance so they come up with various ad-hoc hypotheses to explain it, instead of acknowledging the negative result. This is an hypothesis generating paper, using a highly suspect methods. Not a discovery.

pwdisswordfish2 8y ago

> “If you did a study like ours 100 years ago, the strongest genetic predictor of education would be how many X chromosomes you had, because society was set up in a way that it was much harder for women to get educated than men,” says Benjamin. Likewise, many of the genes that are associated with education today are likely important “because of how today’s educational system is set up. It requires people to sit at desks for hours, and listen to instructions from a teacher. People who get restless, or are less obedient to authority, will fare less well in that environment.” I think the above snip (ha) from https://www.theatlantic.com/science/archive/2018/07/staying-in-school-genetics/565832/ https://www.theatlantic.com/science/archive/2018/07/staying-... is useful in interpreting the results.

wycs 8y ago
I would much prefer direct IQ correlates rather than using education as a proxy for something better measured with IQ tests.
- projectramo 8y ago
  What is “better measured” with IQ tests?
  - laretluval 8y ago
    Intelligence.
    - projectramo 8y ago
      I see so much work before me. Just google it: https://futurism.com/intelligence-changing-what-you-think-you-know-part-one/ https://futurism.com/intelligence-changing-what-you-think-yo...
      - frgtpsswrdlame 8y ago
        Do you have more good info on the subject?

peregrine 8y ago

Has anyone made a tool to run your own 23andme genome data through this and get a score yet?

deleted 8y ago
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jjtheblunt 8y ago
check out promethease.com

xenadu02 8y ago

From the FAQ: > The current study further confirmed the finding from our earlier work that the effects of individual genetic variants on educational attainment are extremely small. The average effect size across the 1,271 genetic variants was just 1.8 weeks of schooling per allele; even the SNPs with the strongest associations only predicted around 3 weeks of additional schooling per allele. Taken together, these 1,271 SNPs accounted for just 3.9% of the variation across individuals in years of education completed. > Here is another way to think about this result. Imagine that we used the results for these 1,271 genetic variants (not the ~1 million SNPs across entire genome we discuss in FAQ 2.3) to predict the educational attainment for a new group of people (separate from our discovery sample). We could then compare each individual’s predicted educational attainment to their actual educational attainment. If we did so, our results suggest that we would find that the predictions and actual outcomes correlate only very modestly (at about r = 0.20). That, in turn, means that if someone were predicted to complete an above average number of years of schooling (i.e., to be in the top half of educational attainment), that person would have about a 58% chance of actually being in the top half of educational attainment. Fifty-eight percent is better than chance (i.e., 50%), suggesting that a prediction based on these 1,271 SNPs has more power to predict educational attainment than a coin flip—but only a bit more power. By contrast, a prediction based on a polygenic score that combines ~1 million SNPs that we studied (see FAQs 1.5 & 2.3) has more predictive power: r = 0.33, corresponding to 11% of the variation across individuals. > The contrast between the 3.9% of the variation predicted by the 1,271 SNPs and the 20% known to be explained by common SNPs (see FAQ 1.7) implies that there are many other SNPs that have not yet been identified. Even larger sample sizes will be needed to identify them. They only included people of European ancestry to eliminate sources of noise and cofounding factors. The effect size is very small, yet it does exist. This seems to prove that intelligence influenced by genetics but is affected by many thousands of genetic variations. There is no "smart" gene, just lots and lots of randomness.

notduncansmith 8y ago
This makes sense. People use different combinations of skills and physical traits to excel in arts, sports, and business. It seems natural then that “intelligence” would encompass a wide range of abilities and traits.

zavi 8y ago

Please don't post Dropbox links, the PDF downloads are unusable on Android.

jjtheblunt 8y ago
Android is confused by PDFs ?