Thread by @ShaiCarmi

Just posted our manuscript "Screening human embryos for polygenic traits has limited utility"

We provide an empirical foundation to the ethical debate regarding the generation of “designer babies” by screening IVF embryos. 1/11

@ehudkar @ToddLencz

biorxiv.org/content/10.110…

Large-scale GWASs yield increasingly accurate polygenic scores (PS), and it is now feasible to calculate such scores from genome-wide data of IVF embryos.

One company is already offering embryo screening for disease risk scores tinyurl.com/yygzdw7q 2/11

It is a short leap to imagine applying this technology outside disease risk. Prospective parents interested in “enhancing” the height or IQ of their future children might seek to generate and genotype IVF embryos, and use only the top-scoring one. 3/11

We addressed the question: Would “polygenic embryo screening” actually work?

If a company ignored any ethical constraints and offered such a service, how much could height and IQ be enhanced compared to an unselected embryo? 4/11

Our study utilized mathematical modeling, simulated data, and real genotype and height data from families with up to 20 grown children each (thanks @dnaxyz @leonidkruglyak biorxiv.org/content/10.110…) 5/11

Our results:

Given current technology, an embryo selected for height would *on average* yield an offspring ~2.5cm taller than randomly selected.

If selecting for IQ, the *average* increase would be ~2.5 points. (Similarity of the numbers is coincidental.) 6/11

We emphasize *average* above, because another key point is that there is great uncertainty in the results for any given set of parents. The error bars around the predicted height/IQ can be much larger than the average increase itself. 7/11

Generating more embryos does not change the results very much. The predicted increase in height (or any other trait) will be small, with large remaining uncertainty, even if it were possible to generate hundreds of embryos. 8/11

In contrast, improving the accuracy of PSs (e.g., by increasing GWAS sizes) will substantially increase the average gain achieved by embryo selection, though uncertainty will again remain large. 9/11

Other factors, including assortative mating, population differences in PS, loss of embryos due to aneuploidy, and pleiotropic effects, will further reduce the expected utility of polygenic embryo screening for a single trait. 10/11

We emphasize that our manuscript is strictly empirical in nature, and is not intended as an ethical opinion. It is meant to provide an evidence-based foundation for the discussion of “designer babies” by the public and policy-makers. 11/11