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>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

>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.)
- frgtpsswrdlame 8y ago
  If what we're interested in is genetic causation then the relevant comparison is to John if he was still shorter but joined the basketball team anyways. In that case the variance between their skills would be less and yet no genes were changed. That illustrates that the original difference wasn't due to genetic but rather environmental factors. >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.
  - JamesBarney 8y ago
    You are using a definition of genetic causation that is not used by anyone in the field of genetics. 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. 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.
    - thraway180306 8y ago
      May that be because this isn't field of genetics at all, but unrelated one called "behavioural genetics" (using quantitative methods of the social sciences, with similar levels of signal, and none of the certainty of actual genetics) wherein Turkheimer formulated the so called "three laws" not unaligned with GP's point?

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.)

frgtpsswrdlame 8y ago
If what we're interested in is genetic causation then the relevant comparison is to John if he was still shorter but joined the basketball team anyways. In that case the variance between their skills would be less and yet no genes were changed. That illustrates that the original difference wasn't due to genetic but rather environmental factors. >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.
- JamesBarney 8y ago
  You are using a definition of genetic causation that is not used by anyone in the field of genetics. 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. 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.
  - thraway180306 8y ago
    May that be because this isn't field of genetics at all, but unrelated one called "behavioural genetics" (using quantitative methods of the social sciences, with similar levels of signal, and none of the certainty of actual genetics) wherein Turkheimer formulated the so called "three laws" not unaligned with GP's point?