As a genetic epidemiologist who has helped develop polygenic risk scores (PRS) for common, multifactoral diseases, I have... thoughts on the launch of a company to provide pre-pregnancy counseling & preimplantation screening based on these PRS. https://www.orchidhealth.com/ 

1) The science doesn’t add up. 2) There are better ways to ensure your (and other) children have healthy and happy lives. 3) The message it sends is… not good.

1) The science doesn’t add up: Exhibit A. We have established the association between these PRS and common, complex, treatable and preventable late-onset diseases like breast and prostate cancer and type 2 diabetes, but…

…we don’t know what the variants in these PRS are doing, biologically. We *are* confident that many of these variants influence many traits, though. So selecting for/against Trait A will also select for/against Traits B,C,D… in ways we don’t understand.

1) The science doesn’t add up: Exhibit B. At least some of the association between PRS and multifactoral disease is due to confounding by social factors or context-dependent. https://twitter.com/genandgenes/status/1380272038351355906?s=20

So waving a magic wand and changing some of these variants at birth may not do anything at all.

1) Science doesn’t add up: Exhibit C. Conditional on parents’ genotypes, these PRS may not explain that much variability in risk. For many couples, the expected gain is much smaller than the average expected gain. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957074/

Moreover, the lifetime risks for some of these diseases is quite low, even for those with the highest PRS.

2) There are better ways to ensure children grow up healthy. Ensure broad access to healthy food & physical-activity-friendly environments. Ensure people with schizophrenia have access to care. Combat stigma associated with mental illness.

3) The message it sends is… not good. As noted in a recent review on polygenic embryonic screening: “an important legacy of eugenics should be awareness that arguments from beneficence can serve as cover for less laudable intentions.” https://pubmed.ncbi.nlm.nih.gov/33106616/ 

“Eugenics was more than a system of state-imposed directives… it was a broadbased ideology incorporating elements of scientific optimism, genetic essentialism, and racism that are still common in the American psyche.”

E.g. this. No, this is not how PRS work. And it’s troubling that Orchid’s founder retweeted this without comment.

To close, this highlights the urgency of developing governance for polygenic embryonic screening, as argued by @ShaiCarmi @GLMbioethics @ToddLencz & @_StaceyPereira in that @GIMJournal price. /fin