The use of polygenic risk scores in pre-implantation genetic testing: an unproven, unethical practice
Forzano F,Antonova O,Clarke A,de Wert G,Hentze S,Jamshidi Y,Moreau Y,Perola M,Prokopenko I,Read A,Reymond A,Stefansdottir V,van El C,Genuardi M,Executive Committee of the European Society of Human Genetics,Public and Professional Policy Committee of the European Society of Human Genetics
Committee members:Borut Peterlin, Carla Oliveira, Karin Writzl, Gunnar Douzgos Houge, Christophe Cordier, Heidi Howard, Milan Macek, Béla Melegh, Alvaro Mendes, Dragica Radojkovic, Emmanuelle Rial-Sebbag, Fiona Ulph, Yalda Jamshidi, …
Forzano, F., Antonova, O., Clarke, A., de Wert, G., Hentze, S., Jamshidi, Y., Moreau, Y., Perola, M., Prokopenko, I., Read, A., Reymond, A., Stefansdottir, V., van El, C., Genuardi, M., Executive Committee of the European Society of Human Genetics, & Public and Professional Policy Committee of the European Society of Human Genetics (2022). The use of polygenic risk scores in pre-implantation genetic testing: an unproven, unethical practice. Eur J Hum Genet. https://doi.org/10.1038/s41431-021-01000-x
Forzano F, Antonova O, Clarke A, de Wert G, Hentze S, Jamshidi Y, Moreau Y, Perola M, Prokopenko I, Read A, Reymond A, Stefansdottir V, van El C, Genuardi M; Executive Committee of the European Society of Human Genetics; Public and Professional Policy Committee of the European Society of Human Genetics. The use of polygenic risk scores in pre-implantation genetic testing: an unproven, unethical practice. Eur J Hum Genet. 2022. doi:10.1038/s41431-021-01000-x
Forzano, Francesca, et al. "The use of polygenic risk scores in pre-implantation genetic testing: an unproven, unethical practice." Eur J Hum Genet, 2022.
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RRM Academy Synopsis
Polygenic risk scores for embryo selection are unproven
Testing embryos with polygenic risk scores is unproven, European geneticists say. A 2022 position statement from the European Society of Human Genetics finds no clinical research on these scores in embryos. The authors ask for a public debate before wider use.
Study at a glance, position statement: European geneticists say embryo polygenic scores are unproven. Source: Forzano F et al., 2022, PMID 34916614.
Key Findings
The statement reports that no clinical research has assessed how well polygenic risk scores diagnose disease risk in embryos.
Scores capture only part of a trait's inherited component. The genome-wide studies behind them are typically done in populations of one ancestry, commonly European, so results may not apply to others.
Embryos from one family vary less than a general population does, and few viable embryos are usually available, so a score is unlikely to help choose between them.
A single genetic variant may raise the risk of one trait while lowering the risk of another. People who request a score are typically told only about the trait they asked about.
The authors call embryo selection by polygenic score premature at best and ask for a societal debate on which traits are acceptable to select.
Interpretation
The paper is a position statement from two committees of the society, and all members reviewed and endorsed it. The paper presents no original study data. Their limits on polygenic scores are general genetics arguments. Their conclusion that embryo use is unproven rests on the lack of clinical research. They call applying adult results to embryos improper and say validation would take many years.
RRM Context
Private companies market polygenic scoring to parents using IVF. IVF bypasses the reasons a couple has trouble conceiving without establishing them. Restorative reproductive medicine works from a different principle: evaluate both partners, find the cause, and treat it. A risk score ranks embryos and evaluates neither partner's fertility.
Our editorial summary of this paper, not the article's abstract.
Abstract
Polygenic risk score analyses on embryos (PGT-P) are being marketed by some private testing companies to parents using in vitro fertilisation as being useful in selecting the embryos that carry the least risk of disease in later life. It appears that at least one child has been born after such a procedure. But the utility of a PRS in this respect is severely limited, and to date, no clinical research has been performed to assess its diagnostic effectiveness in embryos. Patients need to be properly informed on the limitations of this use of PRSs, and a societal debate, focused on what would be considered acceptable with regard to the selection of individual traits, should take place before any further implementation of the technique in this population.
Ethics and Policy › Reproductive Ethics › Genetic Testing of Embryos · Assisted Reproduction › Add-Ons and Adjuncts › Preimplantation Genetic Testing
Francesca Forzano, Olga Antonova, Angus Clarke, Guido de Wert, Sabine Hentze, Yalda Jamshidi, Yves Moreau, Markus Perola, Inga Prokopenko, Andrew Read, Alexandre Reymond, Vigdis Stefansdottir, Carla van El, Maurizio Genuardi
Borut Peterlin, Carla Oliveira, Karin Writzl, Gunnar Douzgos Houge, Christophe Cordier, Heidi Howard, Milan Macek, Béla Melegh, Alvaro Mendes, Dragica Radojkovic, Emmanuelle Rial-Sebbag, Fiona Ulph
F Forzano, O Antonova, A Clarke, G Wert, S Hentze, Y Jamshidi, Y Moreau, M Perola, I Prokopenko, Andy Read, Drew Read, A Read, A Reymond, V Stefansdottir, C El, M Genuardi, B Peterlin, C Oliveira, K Writzl, G Houge, C Cordier, H Howard, M Macek, B Melegh, A Mendes, D Radojkovic, E Rial-Sebbag, F Ulph
PMID 34916614 34916614 DOI 10.1038/s41431-021-01000-x 10.1038/s41431-021-01000-x Forzano et al. 2022, Forzano 2022
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