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I really like the food analogy here. This is a perfect explanation for why embryo selection using this method would absolutely fail. Polygenic scores are touted
by Fusionnex 4y ago
I really like the food analogy here. This is a perfect explanation for why embryo selection using this method would absolutely fail. Polygenic scores are touted as this magic bullet for understanding the contribution of genetics to a phenotype but are utterly imperfect models for what actually occurs due to pleiotropy and epigenetics (among other things). In my opinion the best way for embryo selection is to just have a lot of offspring. Let natural selection do it's job. It gave us us after all.
- MontyCarloHall 4y ago> Polygenic scores are touted as this magic bullet for understanding the contribution of genetics to a phenotype but are utterly imperfect models for what actually occurs due to pleiotropy and epigenetics Agreed! To be a bit more charitable to polygenic scores, they can be mediocre descriptive models—given a real individual’s genotype, they can sometimes decently predict their phenotype (if you consider explaining ~10% of phenotypic variance “decent”). They are unequivocally horrible generative models—you will not obtain a synthetic genotype that would result in a desired phenotype by sampling from a PGS model, i.e. by randomly maximizing the number of high-scoring PGS alleles in a synthetic genome, as proposed by the article.
- Fusionnex 4y agoI like the contrast between descriptive vs generative here. Really puts this into context. If you want to understand the contribution of any particular allele PGS is reasonable. But using PGS to generate a phenotype violates so many assumptions.