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No evidence for using polygenic risk scores in embryo selection

Eleanor Gallegos

Progress Educational Trust

01 February 2022

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[BioNews, London]

The use of polygenic risk scores (PRSs) to select embryos is being advertised and sold by some private fertility clinics.

Such clinics have claimed that PRSs for an embryo can help to predict the likelihood of the future child developing certain conditions or complex traits, when these are thought to be influenced by multiple different genes. However, a paper published in the European Journal of Human Genetics states that there is no evidence that PRSs can reliably anticipate an individual's characteristics in this way.  The paper argues that the use of PRSs to select embryos is both unproven and unethical.

'Many conditions are caused by a combination of genetics and environment, and PRSs are only able to capture parts of any of the relevant genetic component, which is itself likely to be highly complex and difficult to analyse,' said Dr Francesca Forzano, first author of the paper and chair of the European Society of Human Genetics (ESHG)'s Public and Professional Policy Committee. 'In addition, while PRSs may identify individuals at risk of a given disease in the general population (where the genetic variability is very wide) there is no evidence that they can be useful for a couple in determining the choice of one embryo over another, as the genetic variability within an individual family is limited.'

Individuals have different variants of particular genes. PRSs looks at variants, across multiple genes, which can influence the development of a disease or trait. Certain variants may increase the likelihood of developing a particular trait, while others may decrease the likelihood.

A PRS for a particular trait in a particular individual takes what we currently know about genetic variants in a particular population of people, and then predicts where the individual is likely to fall in the distribution of the trait across the entire population. (For example, if the trait in question is height, the PRS might predict whether the individual is likely to be among the tallest 20 percent of the population, the shortest 20 percent of the population, or somewhere in the middle.)

The UK's fertility regulator - the Human Fertilisation and Embryology Authority (HFEA) – told the Times: 'The use of PRSs in pre-implantation genetic testing is currently illegal in the UK. Embryo selection is only legal in the UK to avoid serious inherited illnesses.'

Sarah Norcross, director of the charity Progress Educational Trust, which publishes BioNews, called for regulators to keep a careful eye on the marketing of these tests in the UK. 'It is neither scientifically nor ethically legitimate to try to select embryos using PRSs,' she said. 'Even if – for the sake of argument, and despite a complete lack of clinical evidence – a PRS could meaningfully predict certain things about certain embryos, the sheer number of embryos that would be needed to make use of this test could not be achieved in a clinical setting. There are precious few embryos to choose from in a fertility treatment context, and so reasons for preferring one embryo over another must be grounded in clear evidence.'

SOURCES & REFERENCES

Avoid 'unproven and unethical' polygenic risk scores in embryo selection, say genetics experts
The BMJ |  26 January 2022
Patients warned against American clinics offering 'unethical' embryo screening
The Times |  25 January 2022
The use of polygenic risk scores in pre-implantation genetic testing: an unproven, unethical practice
European Journal of Human Genetics |  17 December 2021
The use of polygenic risk scores in pre-implantation genetic testing; an unproven, unethical practice, says ESHG
The European Society of Human Genetics |  17 December 2021
UK government advisers call for 'proactive regulation' around genomics
The Guardian |  26 January 2022
‘Unproven and unethical’: experts warn against genetic embryo tests
The Guardian |  25 January 2022



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Date Added: 01 February 2022   Date Updated: 01 February 2022
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