This is a truly excellent overview of the state of a field I have been obsessed with since starting grad school. For me, the individual-level variability and low phenotypic variance explained make it hard for me to see a future for PRSs. But you present a nice positive case — particularly about how PRS uncertainty compares to already widely used clinical risk scores
This was fascinating. Thanks. I'm reading this from the place of a clinician, though, and I can only imagine what it will feel like to parents of two-day-old newborns to hear "Congratulations on your new baby! Here are the hundreds of genetic diseases he is susceptible to based on his whole-genome-sequencing!" Also, regarding unknowns, IVF pregnancy has risk factors above spontaneously conceived pregnancy that no one on the genetic frontier seems to be acknowledging. I wrote about it here: https://open.substack.com/pub/annledbetter/p/why-i-dont-fear-an-ivf-takeover?r=8c5pl&utm_campaign=post&utm_medium=web&showWelcomeOnShare=false
I agree. The arguments presented by embryo selection companies are not very well-balanced. For the vast majority of prospective parents, embryo selection based on genetic screening makes little practical sense. most cases, the uncertainty introduced by IVF itself outweighs any potential advantage from selecting one embryo out of ten using PRSs. The main exception, of course, is for carriers of known pathogenic mutations.
This is a truly excellent overview of the state of a field I have been obsessed with since starting grad school. For me, the individual-level variability and low phenotypic variance explained make it hard for me to see a future for PRSs. But you present a nice positive case — particularly about how PRS uncertainty compares to already widely used clinical risk scores
This was fascinating. Thanks. I'm reading this from the place of a clinician, though, and I can only imagine what it will feel like to parents of two-day-old newborns to hear "Congratulations on your new baby! Here are the hundreds of genetic diseases he is susceptible to based on his whole-genome-sequencing!" Also, regarding unknowns, IVF pregnancy has risk factors above spontaneously conceived pregnancy that no one on the genetic frontier seems to be acknowledging. I wrote about it here: https://open.substack.com/pub/annledbetter/p/why-i-dont-fear-an-ivf-takeover?r=8c5pl&utm_campaign=post&utm_medium=web&showWelcomeOnShare=false
I agree. The arguments presented by embryo selection companies are not very well-balanced. For the vast majority of prospective parents, embryo selection based on genetic screening makes little practical sense. most cases, the uncertainty introduced by IVF itself outweighs any potential advantage from selecting one embryo out of ten using PRSs. The main exception, of course, is for carriers of known pathogenic mutations.