The European Society
of Human Genetics

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The use of polygenic risk scores in pre-implantation genetic testing; an unproven, unethical practice, says ESHG

Despite there being no evidence that polygenic risk scores1 (PRSs) can predict the likelihood of as-yet unborn children being liable to a specific disease in the future, some private fertility clinics have begun to sell PRS analyses on embryos to prospective parents.  This practice raises many concerns, says the European Society of Human Genetics in a paper published today (Friday 17 December) in the European Journal of Human Genetics*.

While it is quite normal for parents to consider any genetic risks they may pass to their children, this would usually be done by performing genetic testing for chromosome anomalies or single gene related conditions. In these cases, the ability of the test to predict the development of the disease in any offspring is high.

PRSs are a completely different matter. Many conditions are caused by a complex combination of genetics and environment, and PRSs are only able to capture parts of the relevant genetic component.  And when applied to selecting embryos for transfer in IVF, the PRS will relate to an individual family rather than to a wide population, and therefore will not be very useful in determining the choice of one embryo over another.

In addition, they have never undergone clinical trials to test their diagnostic effectiveness in embryos. Research on PRSs aims rather to contribute to the understanding of disease mechanisms and, perhaps more speculatively, to the management and treatment of liveborn, mostly adult, individuals. In fact, such trials in embryos would be wellnigh impossible, given that one might have to wait decades for the predicted disorder to appear (or not).

So, at present, performing a PRS test for embryo selection would be premature, at best. Adequate, unbiased information on the risks and limitations of this practice should be provided to prospective parents and the public. And it is vital that a societal debate takes place before any potential application of the technique in embryo selection.  Such a debate should be focused on what would be considered acceptable with regards to the selection of individual traits, in particular. Without proper public engagement and oversight, the practice of implementing PRS tests for embryo selection could easily lead to discrimination and the stigmatisation of certain conditions.

At a time when healthcare resources are under strain, it is important that the limited money available should be spent on tests that are known to be effective. Currently, research resources would be better spent on improving knowledge about how PRSs interact with the environment in which we live, rather on the premature application to our future children of an inadequately assessed test with potentially misleading results.

1A polygenic risk score reflects an individual’s estimated genetic predisposition to a given disorder and can be used in predicting the likelihood of that individual developing the disorder