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This transcript was edited for simplicity.

welcome Impact factor, the weekly dose of comment on your new medical examination. I am Yale Medical School doctor F. My name is Perry Wilson.

Imagine that you are going to start a family. Would you like to choose your child’s ability to choose cystic fibrosis? Would you choose if that first child was a boy or a girl? Can you choose his height? Her hair color. His risk of diabetes.

These questions have been around since the trial of the first bioethicist in the university classroom, but only now has technology reached the point where we need to consider the practical implications of answering them.

This week, a New England Journal of Medicine: special report by Daniel Benjamin և his team highlights how the use of polygenic risk points in in vitro fertilization can lead to literal Brave New World situation:

By the way, this is not theoretical. Right now, there are many companies out there that will carry out genetic sequencing on fertile embryos to predict the likelihood of all kinds of diseases for parents. This is a public booklet from a company called Genomic Prediction that shows how parents can use information to choose between two possible embryos.



Source: Clinical Laboratory of Genomic Prediction

Let’s talk about how science works.

Examination of monogenic properties such as cystic fibrosis, sickle cell disease, and things like Tay-Sachs has been around for a long time. And for people who have undergone in vitro fertilization, it is common practice to examine the embryos for these conditions. Remember that in vitro fertilization procedures produce many embryos, not all of which will be implanted, allowing future parents to make some informed choices.

Most of us do not see a big moral problem here. The embryos will be destroyed, so it seems reasonable to choose one that provides a life opportunity for his parents.

But most properties are not homogeneous. I’m not that tall because I have a certain gene that says so. I am my height because many genes work with complex eggs because of my growing environment.

Polygenic risk units combine the genetic information of many genes, sometimes thousands of genes, to form a single number to predict a complex trait.

Let’s start with the controversial IQ.

2018 Nature: Genetics published an article looking at the genomes of some 270,000 people of European descent. Gene variants were associated with individual performance on the IQ test. What you see here, known as the Manhattan Plot, is how strongly the different genetic variants are associated with IQ.



Savage JE, et al. Nat Genet. 2018; 50: 912-919:

You can immediately tell that there is no gene that can tell what your IQ will be like. In fact, this study found about 1,000 genes linked to IQ.

The authors could then look at that individual, see which of those 1,000 genetic variants they had, and combine them to create a single number, the genetic score of IQ.

This genetic assessment is correlated with the actual IQ at a ratio of 0.23, which is normal but not high. This means that about 94% of IQ fluctuations are accounted for by items other than genetic assessment.

He said, “What if you had to choose between five embryos for fertilization? I gave you five points of polygenic risk for intelligence.” Which would you choose?


Not so fast. In: New England Journal: The manuscript does something important here, which is to say, “Stand up, these units are not for that.” They may not even work in the fertilized plant.

Why? Several reasons.

The biggest thing is that all the embryos you choose are native. These polygenic risk points come from the population of unrelated individuals. The genetic diversity of Europe is much bigger than the genetic diversity of my three children.

In the picture I showed you, you have five embryos that show one standard deviation of IQ from the average population in any direction. It is unlikely that the couple’s embryos are so diverse. Most likely, you will get something like this.


The marginal benefit of any polygenic risk assessment is sharply reduced in genetically linked embryos.

The authors of NEJM modeled this using the polygenic risk assessment for educational attainment.



New England Journal of Medicine: © 2021

They compared the use of polygenic assays to simply randomly selecting an embryo in red, assuming that all the embryos were from different families. Using a risk assessment, on average, gives you about 1.5 years of additional educational achievement. In the family, however, it is much less. 0.55 years. And that is of European origin, because that is where the unit was developed. It is even worse for people of other backgrounds.

And look at those standard deviations. Huge So sure, maybe if you are of European descent, using a polygenic risk assessment will, on average, lead you to choose an embryo that will receive an extra semester of educational achievement, but you will often do worse. Here is what the distribution really is.


But hey, I got it. More information is better, isn’t it? Can you maximize the odds?

It is not necessary that. The authors point to another problem with polygenic risk assessments: pleiotropy. The idea here is that genes do not do just one thing, nor do polygenic risk units. For example, the score of educational attainment is not only related to the level of higher education, but also to the high risk of bipolar disorder.


Do companies disclose these links when advising parents?

We have two major problems here. There is an ethical elephant in the room. If you can afford to pay for your child’s smart choice, should you be able to? Could it be that the environmental inconsistencies in our society are taking root, turning them into actual genetic inconsistencies? It ‘s a terrible idea.

But, fortunately, science is not good enough. The use of polygenic risk assessments for embryo selection is, at the moment, a “one-size-fits-all” situation that gives individuals a sense of control over which they still have little control over. Offering control over the uncontrollable is a great business plan, make no mistake. But this is not an existential threat.

The big question for me is how much better we will get at it. I am not a genetic determinant. There is a limit to our ability to predict results based on genetics alone. But we have not reached that yet. What will the world, our children, look like when we do?

F. Perry Wilson, MD, MSCE, Associate Professor of Medicine տնօրեն Director of Yale’s Clinical and Translational Research Accelerator. His scholarly work can be found in the Huffington Post, NPR, and here at Medscape. He tweets @fperrywilson: : Hosts its liaison database at www.methodsman.com.

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