I’m happy to read any evidence to the contrary, but my current view is that for most traits, the genetic variants that only have effects in certain environments that are no longer present are pretty unusual. And even in the cases where this is true, it will only slightly reduce the effect size from editing.
You’re correct about GWAS only showing associations, but there are ways around this. For one thing, you can use sibling validation to narrow down the set of variants to direct causal impacts rather than genetic nurture, for example, and you can use finemapping and other techniques to reduce uncertainty about which SNP in a clump is actually causing the effect.
And after all that, you can just sort the genes to edit by effect size * probability of being causal when deciding edit priority.
I’m happy to read any evidence to the contrary, but my current view is that for most traits, the genetic variants that only have effects in certain environments that are no longer present are pretty unusual. And even in the cases where this is true, it will only slightly reduce the effect size from editing.
You’re correct about GWAS only showing associations, but there are ways around this. For one thing, you can use sibling validation to narrow down the set of variants to direct causal impacts rather than genetic nurture, for example, and you can use finemapping and other techniques to reduce uncertainty about which SNP in a clump is actually causing the effect.
And after all that, you can just sort the genes to edit by effect size * probability of being causal when deciding edit priority.