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.
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.
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, ...
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.
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.)
>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.
When genes cause changes 'outside the skin' the way those outside changes affect your skill are environmental changes by definition. For example you're saying that in our current society, where you can choose your extracurricular activity, the difference in their basketball-skill that's attributable to genetics is x. But in a different society where high school basketball practice was state mandated the difference in their basketball-skill that's attributable to genetics would be y where y < x. The difference between x and y can't be caused by genetics because we haven't changed any genes so it shows that we were just misestimating genetic causation to begin with.
Growth hormone influences height, imagine a world where everyone's level of growth hormone is regulated. Suddenly all of these growth hormone influencing genes no longer have any effect on height. By your definition growth hormone does not genetically cause height because of this hypothetical. You could see how using a definition is both incredibly restrictive as well as almost impossible to measure, and therefore not a very useful definition.
That's worrying.
>It sounds like your definition is "Is there any hypothetical environment where the phenotypic expression of a gene could be changed?" The answer is almost always yes.
Sure but we don't even need a hypothetical environment where high school basketball practice is state-mandated, we just need any hypothetical environment where John and Jim both go to basketball practice and their genes stay the same to see that what is labeled as genetic causation is actually environmental. I mean are you telling me the entire field has no way to distinguish a skill->environment->skill feedback effect from a genes->skill effect?
I'd say that genes seem essentialist, they're something that defines you and can't be changed but environment isn't that way, it's malleable and can be changed. So take this example, we're gonna say at least 11% of IQ is genetic, right? But if we pass some laws so that we have better teachers and smaller class sizes and better remedial programs then what IQ is only 8% genetic? Or even in the case that the laws help the top more and IQ expands to 14% genetic. In that case it doesn't seem that our measurements of genetics effects were accurately measuring the genetics at all, just environmental effects that are hard to account for.
>You could see how using a definition is both incredibly restrictive as well as almost impossible to measure, and therefore not a very useful definition.
Yes, I agree that what I'm saying would make genetic causation very difficult to measure. But it's also the truth about what genetic causation is. Instead we're just opting for what is easy to measure and labeling it as the thing that is hard to measure. That's not right.
Can you describe how you would even hypothetically measure your definition of "genetic causation"? Could you give an example of a "gene causing" the expression of an interesting trait in a way that is immune to environmental changes?
You're looking for a gene that causes an outcome completely independently of all environments. I don't think this exists for any interesting traits. Not to mention how much effect a change has on a given trait is dependent on the genetic make up of the population.
> But it's also the truth about what genetic causation is. No it's not, everyone who talks about genetic causation seriously use a different definition. I don't know why your own personal definition is better than the definition used by every single person who studies genetics.
With my method you can still say that no matter the environment gene x does this thing which can interact with gene y or gene z or environmental factors a, b, c in certain ways.
I think that proving intelligence is XX% genetic is basically meaningless since we can't actually remove environmental effects and if I'm really honest I think it's popularity in the culture is usually driven by spurious motives.
>No it's not, everyone who talks about genetic causation seriously use a different definition. I don't know why your own personal definition is better than the definition used by every single person who studies genetics.
Why do you think this is at the top of Hacker News? Because people's common understanding of a title like:
New study shows that IQ is 11% genetic
Is that at least 11% of their intelligence comes straight from their DNA, not that actually we could change 11% to 5% or 8% or 17% or most any number we want just by changing some laws or fortifying food or any number of environmental changes. The popularity of genetics research in popular media requires this bait-and-switch about what is actually being (mis) measured.
> With my method you can still say that no matter the environment gene x does this thing which can interact with gene y or gene z or environmental factors a, b, c in certain ways.
If you arguing that it is better to understand all of the casual pathways a gene influences a trait than to not understand that, then I strongly agree. If you are arguing that understanding which genes casually influence which complex traits is useless until we know all of the casual pathways that gene affect a trait then I'll have to disagree just as strongly.
> I think that proving intelligence is XX% genetic is basically meaningless since we can't actually remove environmental effects and if I'm really honest I think it's popularity in the culture is usually driven by spurious motives.
First proving what % of intelligence is heritable is not the purpose of GWAS's. Twin studies are used for this, and they've found that intelligence is highly heritable.(far higher than 11%)
Ways that GWAS's are useful without removing environment effects.
- Embryo selection
- Tests to figure out risk for certain diseases for preventative purposes
- Used to figure out what are important pathways in complex traits/disease. For instance if everyone with a certain defective enzyme has a 50% reduction in heart attacks this could lead to a drug candidate
> New study shows that IQ is 11% genetic > Is that at least 11% of their intelligence comes straight from their DNA, not that actually we could change 11% to 5% or 8% or 17% or most any number we want just by changing some laws or fortifying food or any number of environmental changes. The popularity of genetics research in popular media requires this bait-and-switch about what is actually going on.
If you are arguing that some people(maybe even a lot) misunderstand the definition of genetic causation in a similar way that you previously did, then that might be true. But when any experts, or any study talks about genetic causation they are using the definition the rest of us are using on the this thread.
And yet here we are on a thread about using a GWAS to prove what % of intelligence is heritable.
>If you are arguing that some people(maybe even a lot) misunderstand the definition of genetic causation in a similar way that you previously did, then that might be true.
My understanding isn't past tense. Here, allow me to illustrate why this makes no sense to me. Let's take what Gwern said above:
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.
But in my basketball example I could also say this:
Are they environmental causation? Yes, because if you counterfactually changed the environment and nothing but the environment, you would get different outcomes. They are differences which make a difference.
So we are going to take factors where both of those statements are true and still assert that they are genetically causal? That's incorrect.
>But when any experts, or any study talks about genetic causation they are using the definition the rest of us are using on the this thread.
The 'rest of us' in this thread are definitely not using the same language you use. Let's take a look at just the post author's comments:
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>The most iron-clad part of showing direct gene->trait causation is the 4 sibling-comparison studies
except it's not iron-clad at all and it doesn't show direct gene->trait causation.
>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
Their environments are not near-identical.
>No, it doesn't. It merely tells us that with the data up to now, we've reached 11% (up from, incidentally, ~0.3% just 5 years ago). It provides a very loose lower bound on genes.
Except you're telling me that not only is a GWAS not useful for this purpose but that even this number shouldn't be treated as a 'lower bound' but as a potential identifier to further study the genes identified. It would seem that this
>> Observational studies of this type cannot show causality >They can: sibling comparisons.
Again, this quote appears to conflict with what you believe GWASs are capable of.
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Again, why are these falsehoods being spread around? Because of an (mis)understanding that 'genetic causation' as measured in the paper is not manipulatable by the environment. Except that it actually is. And a misunderstanding of what GWASs are good for.
>- Embryo selection
No it's not. GWASs don't understand what they're measuring and label the environmental as genetic biasing their measurements. Embryo selection is done the old-fashioned way looking for specific genetic variants that we understand through the use of other types of studies.
>- Tests to figure out risk for certain diseases for preventative purposes
Look at the use of GWASs in identifying schizophrenia. They typically fail to replicate. GWASs find genetic connections where none exist.
Take schizophrenia. It could be that we run a GWAS on schizophrenia and find some genetic similarities. Then we look at these similarities and find one of them is a cuddle gene. A cuddle gene what the heck? Well the cuddle gene makes you want to cuddle which makes their mothers more likely to own pets to cuddle which makes them more likely to own cats which increases their risk of exposure to toxoplasmosis which increases their of schizophrenia. Is that a genetic causation? Because the way genetic causation is actually being used in this thread really doesn't lead to that conclusion. It leads to the idea that the identified genes make you a little more unstable in a certain way, not that we could totally eliminate that element of genetic causation by just educating mothers.
So, it might just be both environment and the genetic influence both correlating to the same thing, and they admit as much.
After high correlates are found, further experiments will disentangle the relationship.