7 ms·

> But the idea here is that, by checking thousands of genes, you can make predictions for things that start to be very relevant to parents, like attractiveness

> But the idea here is that, by checking thousands of genes, you can make predictions for things that start to be very relevant to parents, like attractiveness or height or intelligence. Personally, I think this interpretation of polygenic risk scoring is a crock of irreproducible shite. I don’t think it’s your fault, I think a lot of people in the field are shilling something they don’t have for grant money, and they’ve created an exciting sci-fi yarn that’s easy for people outside the field to digest. Height is a univariate trait that does not change after the age of ~20. If you show me someone who can take a genome and predict adult height within a centimeter, then I’ll believe they have a snowball’s chance of predicting something as nuanced and varied as “attractiveness” or “intelligence”. I think there’s promise in applying PRS to assessing risk for non-Mendelian disease, but there’s far too many social and environmental variables at play to reliably predict these softer features. Like other people have joked, if you want a single number that best predicts educational attainment, use a zip code.

s1artibartfast 4y ago
> show me someone who can take a genome and predict adult height within a centimeter, then I’ll believe they have a snowball’s chance of predicting something as nuanced and varied as “attractiveness” or “intelligence”. This has been done. Not to 1cm but ~3cm, and it has been reproduced by many labs all over the world That said, most genetic prediction aren't targeting exact vales, but avoiding the worst outcomes, which is a lot easier. Instead of saying this embryo will go grow to X cm, the claim is this embryo is 90% likely to grow to be taller than average. Same for IQ. They don't predict the IQ, but decrease poor outcomes and increase high ones. Hell, we have had rough monogenic screening for IQ since the 1960s https://arxiv.org/pdf/2101.05870.pdf https://arxiv.org/pdf/2101.05870.pdf
- cauthon 4y ago
  I haven't previously read the Lello paper [1] that review is citing, but a quick skim makes me skeptical. Particulary the legend for figure 5: > Activated SNPs are distributed roughly uniformly throughout the genome. If the authors were actually identifying a genetic component to a heritable trait, I'd expect them to observe some linkage disequilibrium. And without any analysis of the SNPs (are they coding/noncoding? which genes are they associated with?) it's hard to believe that they're uncovering actual biology and not just chance correlates with external/socioeconomic factors. I also find it difficult to trust studies when the lead author fails to disclose a conflict of interest. [2] [1] https://academic.oup.com/genetics/article/210/2/477/5931053 https://academic.oup.com/genetics/article/210/2/477/5931053 [2] https://academic.oup.com/genetics/article/214/1/231/5930514 https://academic.oup.com/genetics/article/214/1/231/5930514
  - s1artibartfast 4y ago
    >it's hard to believe that they're uncovering actual biology and not just chance correlates with external/socioeconomic factors Do you think no biological basis exists? Either way, they are still correlates, even if some aren't causative. These models are still predictive when tested against control groups outside the training population.
    - cauthon 4y ago
      Yes, I think height is a heritable trait. Understanding whether the model is capturing biology is critical when thinking about applying it to IVF. If the model is primarily capturing socioeconomic correlates, those factors will (in most cases) be fixed for all embryos from a given pair of parents. The PRS needs to be weighting _biological_ risk conditioned on a fixed environment if its to be used ethically in this context.
      - s1artibartfast 4y ago
        What are your requirements for ethical use? In what case are you expecting the purchasers to be harmed? It seems reasonable to screen for the other factors as well if a correlation exists.
    - bergenty 4y ago
      There may be but “nature” is strong on atleast this trait. Just look at height differences between north and South Koreans.
      - s1artibartfast 4y ago
        North vs South Korea would be an example of nurture/environment, not nature/genes. An example of Nature would be comparing well fed children of basket ball players vs children of horse jockeys.
        wizofaus 4y ago
- bergenty 4y ago
  The control on those are in places that have relatively standard nutritional distribution. The environment obviously plays a strong role, just look at the height difference in populations between north and South Korea.
ChadNauseam 4y ago
> Height is a univariate trait that does not change after the age of ~20. If you show me someone who can take a genome and predict adult height within a centimeter, then I’ll believe they have a snowball’s chance of predicting something as nuanced and varied as “attractiveness” or “intelligence”. I don't know why that would be the standard, since the amount of variation in height that's attributable to environmental factors might make that fundamentally impossible. But we can get quite close to that standard nonetheless. And even if it's not possible yet, do you think that in 20 years we'll have no ability to predict height or intelligence from a genome? It seems very plausible to me, especially with how cheap genome sequencing is now.
- cauthon 4y ago
  > since the amount of variation in height that's attributable to environmental factors might make that fundamentally impossible Yes, that is my point. Both intelligence and attractiveness have a significant amount of variation attributable to environmental or other external factors, and have the additional complication that they cannot be measured by a single objective unit (like height can). > do you think that in 20 years we'll have no ability to predict height or intelligence from a genome The quantification of intelligence is notoriously confounded by socioeconomic factors. I do not think talking about predicting a feature makes sense while we are currently unable to describe it well. IMO dedicating funding to improving child care, healthcare+diet, and k-12 education will have a much greater impact on increasing a society's measures of intelligence and educational attainment. There's much stronger evidence that these factors are associated with improved outcomes. But, the work isn't "sexy" and doesn't come with a sci-fi flair. Kind of like ignoring climate work in favor of Mars colonization. There seems to be a cultural bias in tech towards moonshot panaceas vs doing the unglamorous grind. It makes me think of the Bill Gates quote that "a lazy person will find an easy way to do a hard job," and while that's valuable in some contexts I don't think it's universally applicable.
  - ROTMetro 4y ago
    Show the military why this is needed and you might get some funding action, that is after all how we got a school lunch program. https://www.ilsna.net/resources/schoolnutrition/historyschoollunch#:~:text=Though%20school%20foodservice%20began%20long,of%20diet%2Drelated%20health%20problems https://www.ilsna.net/resources/schoolnutrition/historyschoo....

s1artibartfast 4y ago

> show me someone who can take a genome and predict adult height within a centimeter, then I’ll believe they have a snowball’s chance of predicting something as nuanced and varied as “attractiveness” or “intelligence”. This has been done. Not to 1cm but ~3cm, and it has been reproduced by many labs all over the world That said, most genetic prediction aren't targeting exact vales, but avoiding the worst outcomes, which is a lot easier. Instead of saying this embryo will go grow to X cm, the claim is this embryo is 90% likely to grow to be taller than average. Same for IQ. They don't predict the IQ, but decrease poor outcomes and increase high ones. Hell, we have had rough monogenic screening for IQ since the 1960s https://arxiv.org/pdf/2101.05870.pdf https://arxiv.org/pdf/2101.05870.pdf

cauthon 4y ago
I haven't previously read the Lello paper [1] that review is citing, but a quick skim makes me skeptical. Particulary the legend for figure 5: > Activated SNPs are distributed roughly uniformly throughout the genome. If the authors were actually identifying a genetic component to a heritable trait, I'd expect them to observe some linkage disequilibrium. And without any analysis of the SNPs (are they coding/noncoding? which genes are they associated with?) it's hard to believe that they're uncovering actual biology and not just chance correlates with external/socioeconomic factors. I also find it difficult to trust studies when the lead author fails to disclose a conflict of interest. [2] [1] https://academic.oup.com/genetics/article/210/2/477/5931053 https://academic.oup.com/genetics/article/210/2/477/5931053 [2] https://academic.oup.com/genetics/article/214/1/231/5930514 https://academic.oup.com/genetics/article/214/1/231/5930514
- s1artibartfast 4y ago
  >it's hard to believe that they're uncovering actual biology and not just chance correlates with external/socioeconomic factors Do you think no biological basis exists? Either way, they are still correlates, even if some aren't causative. These models are still predictive when tested against control groups outside the training population.
  - cauthon 4y ago
    Yes, I think height is a heritable trait. Understanding whether the model is capturing biology is critical when thinking about applying it to IVF. If the model is primarily capturing socioeconomic correlates, those factors will (in most cases) be fixed for all embryos from a given pair of parents. The PRS needs to be weighting _biological_ risk conditioned on a fixed environment if its to be used ethically in this context.
    - s1artibartfast 4y ago
      What are your requirements for ethical use? In what case are you expecting the purchasers to be harmed? It seems reasonable to screen for the other factors as well if a correlation exists.
  - bergenty 4y ago
    There may be but “nature” is strong on atleast this trait. Just look at height differences between north and South Koreans.
    - s1artibartfast 4y ago
      North vs South Korea would be an example of nurture/environment, not nature/genes. An example of Nature would be comparing well fed children of basket ball players vs children of horse jockeys.
      - wizofaus 4y ago
bergenty 4y ago
The control on those are in places that have relatively standard nutritional distribution. The environment obviously plays a strong role, just look at the height difference in populations between north and South Korea.

ChadNauseam 4y ago

> Height is a univariate trait that does not change after the age of ~20. If you show me someone who can take a genome and predict adult height within a centimeter, then I’ll believe they have a snowball’s chance of predicting something as nuanced and varied as “attractiveness” or “intelligence”. I don't know why that would be the standard, since the amount of variation in height that's attributable to environmental factors might make that fundamentally impossible. But we can get quite close to that standard nonetheless. And even if it's not possible yet, do you think that in 20 years we'll have no ability to predict height or intelligence from a genome? It seems very plausible to me, especially with how cheap genome sequencing is now.

cauthon 4y ago
> since the amount of variation in height that's attributable to environmental factors might make that fundamentally impossible Yes, that is my point. Both intelligence and attractiveness have a significant amount of variation attributable to environmental or other external factors, and have the additional complication that they cannot be measured by a single objective unit (like height can). > do you think that in 20 years we'll have no ability to predict height or intelligence from a genome The quantification of intelligence is notoriously confounded by socioeconomic factors. I do not think talking about predicting a feature makes sense while we are currently unable to describe it well. IMO dedicating funding to improving child care, healthcare+diet, and k-12 education will have a much greater impact on increasing a society's measures of intelligence and educational attainment. There's much stronger evidence that these factors are associated with improved outcomes. But, the work isn't "sexy" and doesn't come with a sci-fi flair. Kind of like ignoring climate work in favor of Mars colonization. There seems to be a cultural bias in tech towards moonshot panaceas vs doing the unglamorous grind. It makes me think of the Bill Gates quote that "a lazy person will find an easy way to do a hard job," and while that's valuable in some contexts I don't think it's universally applicable.
- ROTMetro 4y ago
  Show the military why this is needed and you might get some funding action, that is after all how we got a school lunch program. https://www.ilsna.net/resources/schoolnutrition/historyschoollunch#:~:text=Though%20school%20foodservice%20began%20long,of%20diet%2Drelated%20health%20problems https://www.ilsna.net/resources/schoolnutrition/historyschoo....