5 ms·

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 SNP

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
      I suspect that was a mistype based on their other post, it was probably meant to be "nurture"?
    - bergenty 4y ago
      Yep, nurture definitely. Can’t edit it anymore.
  - desmosxxx 4y ago
    Nature can still be important for even highly heritable traits. For example, the size of a person's vocabulary is highly heritable, but a feral human will have very limited vocabulary. Such traits still have a very strong biological basis.
xyzzyz 4y ago
> it's hard to believe that they're uncovering actual biology and not just chance correlates with external/socioeconomic factors. This is routinely validated on siblings. If the polygenic scores are as accurate in predicting differences between siblings (who, presumably, share substantially same environment) as they are between unrelated people, it means that they detect real, biological things, instead of just some kind of population stratification. The linked abstract, of course, mentions this, and you'd have known this if you had read the article. Also, your assumption that socioeconomic factors are independent of genomes (that they are just "chance correlates) is also substantially wrong. Genes correlate with socioeconomic factors, because they often cause socioeconomic factors. People are not born into socioeconomic conditions randomly, they are born into socioeconomic conditions of people who share half of their genome with them.

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
    I suspect that was a mistype based on their other post, it was probably meant to be "nurture"?
  - bergenty 4y ago
    Yep, nurture definitely. Can’t edit it anymore.
- desmosxxx 4y ago
  Nature can still be important for even highly heritable traits. For example, the size of a person's vocabulary is highly heritable, but a feral human will have very limited vocabulary. Such traits still have a very strong biological basis.

xyzzyz 4y ago

> it's hard to believe that they're uncovering actual biology and not just chance correlates with external/socioeconomic factors. This is routinely validated on siblings. If the polygenic scores are as accurate in predicting differences between siblings (who, presumably, share substantially same environment) as they are between unrelated people, it means that they detect real, biological things, instead of just some kind of population stratification. The linked abstract, of course, mentions this, and you'd have known this if you had read the article. Also, your assumption that socioeconomic factors are independent of genomes (that they are just "chance correlates) is also substantially wrong. Genes correlate with socioeconomic factors, because they often cause socioeconomic factors. People are not born into socioeconomic conditions randomly, they are born into socioeconomic conditions of people who share half of their genome with them.