ADVISORY ON THE USE OF POLYGENIC RISK SCORES TO SCREEN EMBROS FOR ADULT MENTAL HEALTH CONDITIONS. 

Approved by the ISPG Board May, 2021

Several private companies are using polygenic risk scores to screen embryos for adult mental health conditions. The screening is done as part of in-vitro fertilization. A polygenic risk score is a single number that measures part of a person’s genetic predisposition for a condition1. These genetic scores are built by adding up the small effects from many hundreds or thousands of genes. Although in general higher scores mean you are more likely to have a condition, many healthy people will have high scores; others might develop the condition even with a low score. The accuracy with which a polygenic score can predict psychiatric illnesses, such as schizophrenia, bipolar disorder and major depression, is currently not sufficient for clinical use. Furthermore, the unintended consequences of its use for embryo selection need to be considered. While polygenic risk scores are used in research, there are currently no clinical uses in psychiatry.

The ISPG views with concern the offering of polygenic embryo screening services for psychiatric conditions, for both scientific and ethical reasons. First, polygenic risk scores do not determine whether a person will develop a condition. They measure just one of many possible risk factors. Second, polygenic risk scores are not specific to a single condition. This means that selection for one condition can affect other genetic traits. Third, it is not known how to accurately communicate the level of risk to prospective parents. Fourth, in many countries, there is no regulation or oversight of polygenic embryo screening to protect against misuse, like there is for other kinds of genetic testing. Fifth, screening embryos for psychiatric conditions may increase stigma surrounding these diagnoses. Finally, psychiatric genetics has a history of misuse for eugenics2-4, and polygenic embryo screening raises many ethical, legal, and social issues that can potentially lead to harm and have not yet been studied or addressed5.

While scientific and ethical issues have been widely studied for single-gene embryo testing6, the issues listed above have not been explored for polygenic embryo screening. The few published polygenic embryo screening studies have been mostly led by a private company selling these services7–11. Public discussion and debate including all potential stakeholders is urgently needed on a national and international scale. Given these considerations, the ISPG urges caution and calls for additional research and oversight on the use of polygenic embryo screening.

For those seeking additional information, we recommend this introduction to polygenic scores from the Broad Institute and this blog post from the National Society of Genetic Counselors.

References:

  1. Wray NR, Lin T, Austin J, et al. From Basic Science to Clinical Application of Polygenic Risk Scores: A Primer. JAMA Psychiatry. Published online September 30, 2020. doi:10.1001/jamapsychiatry.2020.3049
  2. Hoge SK, Appelbaum PS. Ethics and neuropsychiatric genetics: a review of major issues. Int J Neuropsychopharmacol. 2012;15(10):1547-1557. doi:10.1017/S1461145711001982
  3. Brannan C, Foulkes AL, Lázaro-Muñoz G. Preventing discrimination based on psychiatric risk biomarkers. Am J Med Genet. 2019;180(2):159-171. doi:10.1002/ajmg.b.32629
  4. Palk AC, Dalvie S, de Vries J, Martin AR, Stein DJ. Potential use of clinical polygenic risk scores in psychiatry – ethical implications and communicating high polygenic risk. Philos Ethics Humanit Med. 2019;14(1):4. doi:10.1186/s13010-019-0073-8
  5. Lázaro-Muñoz G, Pereira S, Carmi S, Lencz T. Screening embryos for polygenic conditions and traits: ethical considerations for an emerging technology. Genet Med. Published online October 27, 2020. doi:10.1038/s41436-020-01019-3
  6. Sueoka K. Preimplantation genetic diagnosis: an update on current technologies and ethical considerations. Reprod Med Biol. 2016;15(2):69-75. doi:10.1007/s12522-015-0224-6
  7. Treff NR, Eccles J, Lello L, et al. Utility and First Clinical Application of Screening Embryos for Polygenic Disease Risk Reduction. Front Endocrinol (Lausanne). 2019;10:845. doi:10.3389/fendo.2019.00845
  8. Treff NR, Zimmerman R, Bechor E, et al. Validation of concurrent preimplantation genetic testing for polygenic and monogenic disorders, structural rearrangements, and whole and segmental chromosome aneuploidy with a single universal platform. Eur J Med Genet. 2019;62(8):103647. doi:10.1016/j.ejmg.2019.04.004
  9. Treff NR, Eccles J, Marin D, et al. Preimplantation Genetic Testing for Polygenic Disease Relative Risk Reduction: Evaluation of Genomic Index Performance in 11,883 Adult Sibling Pairs. Genes. 2020;11(6):648. doi:10.3390/genes11060648
  10. Karavani E, Zuk O, Zeevi D, et al. Screening Human Embryos for Polygenic Traits Has Limited Utility. Cell. 2019;179(6):1424-1435.e8. doi:10.1016/j.cell.2019.10.033
  11. Lencz T, Backenroth D, Green A, Weissbrod O, Zuk O, Carmi S. Utility of polygenic embryo screening for disease depends on the selection strategy. bioRxiv. Published online November 26, 2020:2020.11.05.370478. doi:10.1101/2020.11.05.370478

Authored By ISPG Ethics Committee:  Chair Lea Davis, Co-Chair Maya Sabatello, Head Writer Todd Lencz, and Contributors: Jehannine Austin, Anna Docherty, Laura Bierut, Gabriel Lazaro-Munoz, Consuelo Walss-Bass, Laura Huckins, Holly Peay, Roseann Peterson, Takahiro Soda, David Crepaz-Keay, David Curtis, Franziska Degenhardt, Manuel Mattheisen, Marcella Rietschel, Bettina Meiser 

All rights reserved.  No part of this statement may be reproduced or used in any manner without written permission from the International Society of Psychiatric Genetics.

Short Title: ISPG Ethics Advisory on Embryo Screening | Keywords: psychiatry, genetics, ethics, testing, polygenic, embryo, risk, scores

Download the PDF: 2021 May ISPG Ethics Advisory Embryo Screening

INTERNATIONAL SOCIETY OF PSYCHIATRIC GENETICS ETHICS COMMITTEE: ISSUES FACING US

Approved by Board October, 2018

https://onlinelibrary.wiley.com/doi/full/10.1002/ajmg.b.32736

Authors: Gabriel Lázaro-Muñoz, Maya Sabatello, Holly Peay, Franziska Degenhardt, Todd Lencz, Takahiro Soda, Bettina Meiser, Laura Huckins, Weiyi Mu, Nicole Martinez-Martin, Consuelo Walss-Bass, Kevin McGhee, Manuel Mattheisen, Joseph McClay, Randell Libby, Anna Docherty, David Crepaz-Keay, Laura Bierut, Jehannine Austin, Roseann Peterson, Lea K. Davis

Short Title: ISPG Ethics Committee | Keywords: psychiatry, genetics, ELSI, ethics, testing