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Problems with Using Polygenic Scores to Select Embryos
Open accessAbstract
Companies have recently begun to sell a new service to patients considering in vitro fertilization: embryo selection based on polygenic scores (ESPS). These scores represent individualized predictions of health and other outcomes derived from genomewide association studies in adults to partially predict these outcomes. This article includes a discussion of many factors that lower the predictive power of polygenic scores in the context of embryo selection and quantifies these effects for a variety of clinical and nonclinical traits. Also discussed are potential unintended consequences of ESPS (including selecting for adverse traits, altering population demographics, exacerbating inequalities in society, and devaluing certain traits). Recommendations for the responsible communication about ESPS by practitioners are provided, and a call for a society-wide conversation about this technology is made. (Funded by the National Institute on Aging and others.).
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“our results do not support any immediate medical or clinical applications, such as polygenic prediction in direct-to-consumer services49,50.”
From Shared genetic architectures of educational attainment in East Asian and European populations (2024) · cites this paper as [49]
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Citations
Cites
Clinical use of current polygenic risk scores may exacerbate health disparities
Martin, A. R., Kanai, M., Kamatani, Y., Okada, Y., Neale, B. M., & Daly, M. J. (2019) · Nature Genetics · doi:10.1038/s41588-019-0379-x · Cited by 2,821 · cited 1×
“When polygenic scores constructed from such studies have been tested on participants who were not of European ancestries, their predictive power was much lower.(10) Figure 1 shows the expected differences in educational attainment between the person with the highest polygenic score among 10 persons and a person select…”
BackgroundSelf-citation23andMe Research Team, Lee, J. J., COGENT (Cognitive Genomics Consortium), Social Science Genetic Association Consortium, Wedow, R., Okbay, A., Kong, E., Maghzian, O., Zacher, M., Nguyen-Viet, T. A., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0147-3 · Cited by 2,470 · cited 1×
“The authors of a recent paper reported that according to current polygenic scoring for educational attainment, the prevalence of college completion is roughly 10% among persons in the lowest quintile and roughly 45 to 60% among those in the highest quintile.(6) Drawing on these differences, advocates have encouraged p…”
BackgroundSelf-citationThe personal and clinical utility of polygenic risk scores
Torkamani, A., Wineinger, N. E., & Topol, E. J. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0018-x · Cited by 1,655
Polygenic risk scores: from research tools to clinical instruments
Lewis, C. M., & Vassos, E. (2020) · Genome Medicine · doi:10.1186/s13073-020-00742-5 · Cited by 1,360
A global overview of pleiotropy and genetic architecture in complex traits
Watanabe, K., Stringer, S., Frei, O., Umićević Mirkov, M., de Leeuw, C., Polderman, T. J. C., van der Sluis, S., Andreassen, O. A., Neale, B. M., & Posthuma, D. (2019) · Nature Genetics · doi:10.1038/s41588-019-0481-0 · Cited by 1,332
Self-citationThe nature of nurture: Effects of parental genotypes
Kong, A., Thorleifsson, G., Frigge, M. L., Vilhjalmsson, B. J., Young, A. I., Thorgeirsson, T. E., Benonisdottir, S., Oddsson, A., Halldorsson, B. V., Masson, G., et al. (2018) · Science · doi:10.1126/science.aan6877 · Cited by 949 · cited 1×
“Second, a sizeable portion of the predictive power of the polygenic score for persons from different families comes from “gene–environment correlation” — that is, persons with high polygenic scores are likely to be raised in family environments that promote educational attainment.(9) For example, such persons are like…”
BackgroundGenetic essentialism: On the deceptive determinism of DNA.
Dar‐Nimrod, I., & Heine, S. J. (2010) · Psychological Bulletin · doi:10.1037/a0021860 · Cited by 744 · cited 1×
“One particularly relevant misconception is “genetic determinism”: potential customers may expect that ESPS guarantees the outcome they want.(12) Furthermore, people tend to neglect variance,(13) and polygenic scores do not capture all sources of genetic variation.”
BackgroundTowards clinical utility of polygenic risk scores
Lambert, S. A., Abraham, G., & Inouye, M. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddz187 · Cited by 586
Educational Reform, Ability, and Family Background
Meghir, C., & Palme, M. (2004) · Working paper series - Institute for Fiscal Studies/Working papers · doi:10.1920/wp.ifs.2004.0410 · Cited by 581 · cited 1×
“org July 1, 2021 85 tion would have a greater effect than many environmental interventions that have been implemented.(45) It seems plausible that some patients who have undergone IVF will find ESPS attractive — more so as the expected gains increase.”
BackgroundEdwards, A., Elwyn, G., Covey, J., Matthews, E., & Pill, R. (2001) · Journal of health communication · doi:10.1080/10810730150501413 · Cited by 502
Communicating uncertainty about facts, numbers and science
van der Bles, A. M., van der Linden, S., Freeman, A. L. J., Mitchell, J., Galvao, A. B., Zaval, L., & Spiegelhalter, D. J. (2019) · Royal Society Open Science · doi:10.1098/rsos.181870 · Cited by 456
Naylor, C., Chen, E., & Strauss, B. (1992) · Annals of Internal Medicine · doi:10.7326/0003-4819-117-11-916 · Cited by 392
Kang, H.-J., Kim, K., & Kim, J. (1997) · Information Processing Letters · doi:10.1016/s0020-0190(97)00039-2 · Cited by 375
The framing effect of relative and absolute risk
Malenka, D. J., Baron, J. A., Johansen, S., Wahrenberger, J. W., & Ross, J. M. (1993) · Journal of General Internal Medicine · doi:10.1007/bf02599636 · Cited by 370
Comparing Within- and Between-Family Polygenic Score Prediction
Selzam, S., Ritchie, S. J., Pingault, J.-B., Reynolds, C. A., O’Reilly, P. F., & Plomin, R. (2019) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2019.06.006 · Cited by 289 · cited 1×
“The attenuation of predictive power within families is likely to be greatest for cognitive and behavioral traits such as educational attainment because the effects of the correlation between genetics and environment and of assortative mating are likely to be greater.(18) As with educational attainment, predictions wil…”
BackgroundA Meta-analysis of the Effects of Presenting Treatment Benefits in Different Formats
Covey, J. A. (2007) · Medical Decision Making · doi:10.1177/0272989x07306783 · Cited by 218
Evidence based purchasing: understanding results of clinical trials and systematic reviews
Fahey, T., Griffiths, S., & Peters, T. J. (1995) · British medical journal · doi:10.1136/bmj.311.7012.1056 · Cited by 209
Bucher, H., Weinbacher, M., & Gyr, K. (1994) · British medical journal · doi:10.1136/bmj.309.6957.761 · Cited by 192
Completeness of reporting trial results: effect on physicians' willingness to prescribe
Bobbio, M., Demichelis, B., & Giustetto, G. (1994) · The Lancet · doi:10.1016/s0140-6736(94)92407-4 · Cited by 188
Screening human embryos for polygenic traits has limited utility
Karavani, E., Zuk, O., Zeevi, D., Barzilai, N., Stefanis, N., Hatzimanolis, A., Smyrnis, N., Avramopoulos, D., Kruglyak, L., Atzmon, G., et al. (2019) · bioRxiv · doi:10.1101/626846 · Cited by 99
Genetic and epigenetic risks of assisted reproduction
Jiang, Z.-R., Wang, Y., Lin, J., Xu, J.-J., Ding, G., & Huang, H. (2017) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2017.07.004 · Cited by 87 · cited 1×
“However, persons contemplating IVF, PGD, or both for the purposes of ESPS should weigh the risks and uncertainties of these technologies to women and their future children.(46,47) Unless and until ESPS is more robustly regulated, companies and clinicians who insist on offering this unproved, societally risky service s…”
BackgroundUtility and First Clinical Application of Screening Embryos for Polygenic Disease Risk Reduction
Treff, N. R., Eccles, J., Lello, L., Bechor, E., Hsu, J., Plunkett, K., Zimmerman, R., Rana, B., Samoilenko, A., Hsu, S., et al. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00845 · Cited by 78 · cited 1×
“These simulation results are, by and large, similar to evidence from sibling pairs.(19,20) Here, we assume that the risk without ESPS corresponds to the lifetime risk in the general U.”
ResultBayefsky, M. J. (2016) · Reproductive Biomedicine & Society Online · doi:10.1016/j.rbms.2017.01.001 · Cited by 75
Utility of polygenic embryo screening for disease depends on the selection strategy
Lencz, T., Backenroth, D., Granot‐Hershkovitz, E., Green, A., Gettler, K., Cho, J. H., Weissbrod, O., Zuk, O., & Carmi, S. (2021) · eLife · doi:10.7554/elife.64716 · Cited by 74 · cited 8×
“The relevant measure is the “expected gain” — that is, the expected difference in the trait (of the person the embryo will become) when choosing the embryo with the highest polygenic score as compared with an embryo selected at random (from the viable embryos), without the use of ESPS.8 We illustrate below how the use…”
InfluentialBu, Z., Chen, Z.-J., Huang, G.-N., Zhang, H.-W., Wu, Q., Ma, Y.-H., Shi, J.-Z., Xu, Y.-W., Zhang, S.-Y., Zhang, C.-L., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0113522 · Cited by 64
Pluripotent Stem Cell-Derived Gametes: Truth and (Potential) Consequences
Mathews, D., Donovan, P., Harris, J. M., Lovell-Badge, R., Savulescu, J., & Faden, R. (2009) · Cell Stem Cell · doi:10.1016/j.stem.2009.06.005 · Cited by 59 · cited 1×
“This caution will be especially important if progress in stem-cell technologies makes it possible to create sperm or egg cells from a person’s blood or skin cells, yielding many more embryos, noninvasively, than is possible today.(43,44)”
BackgroundHow do policymakers update their beliefs?
Vivalt, E., & Coville, A. (2023) · Journal of Development Economics · doi:10.1016/j.jdeveco.2023.103121 · Cited by 50
Heterozygous mutations of growth hormone receptor gene in children with idiopathic short stature.
Bonioli, E., Tarò, M., la Rosa, C., Citana, A., Bertorelli, R., Morcaldi, G., Gastaldi, R., & Coviello, D. (2005) · Growth Hormone & IGF Research · doi:10.1016/j.ghir.2005.08.004 · Cited by 49 · cited 1×
“Consider idiopathic short stature, which has been defined as a height that is more than 2 standard deviations below the mean.(21) A seemingly large risk reduction might not correspond to a very meaningful difference in height because ESPS might result in the selection of embryos that are just over the cutoff point.”
BackgroundBayefsky, M. J., & Berkman, B. (2021) · American Journal of Bioethics · doi:10.1080/15265161.2020.1867933 · Cited by 39
Wilkinson, J., Malpas, P., Hammarberg, K., Tsigdinos, P. M., Lensen, S., Jackson, E., Harper, J., & Mol, B. (2019) · Fertility and Sterility · doi:10.1016/j.fertnstert.2019.09.028 · Cited by 36
Embryo biopsy and development: the known and the unknown.
Zacchini, F., Arena, R., Abramik, A., & Ptak, G. (2017) · Reproduction · doi:10.1530/rep-17-0431 · Cited by 34
Who Should Regulate Preimplantation Genetic Diagnosis in the United States?
Bayefsky, M. J. (2018) · AMA journal of ethics · doi:10.1001/amajethics.2018.1160 · Cited by 30
PREIMPLANTATION GENETIC TESTING: Preimplantation genetic testing for polygenic disease risk
Treff, N. R., Marin, D., Lello, L., Hsu, S., & Tellier, L. C. A. M. (2020) · Reproduction · doi:10.1530/rep-20-0071 · Cited by 27 · cited 1×
“These simulation results are, by and large, similar to evidence from sibling pairs.(19,20) Here, we assume that the risk without ESPS corresponds to the lifetime risk in the general U.”
ResultPergament, D., & Ilijic, K. (2014) · Journal of Clinical Medicine · doi:10.3390/jcm3041437 · Cited by 24
Federal Trade Commission staff concerns with assisted reproductive technology advertising.
Katz, M. A. (1995) · Fertility and Sterility · doi:10.1016/s0015-0282(16)57648-1 · Cited by 12 · cited 1×
“The FTC should help establish what counts as adequate evidence to support claims about the expected gains of ESPS and what counts as adequate information disclosure in this context, as it did in the 1990s and 2000s in curbing the practice of IVF clinics that provided misleading rates of successful pregnancies.(30) In…”
Kraft, S. A., Porter, K. M., Duenas, D. M., Sullivan, E., Rowland, M. G., Saelens, B., Wilfond, B., & Shah, S. K. (2020) · JAMA Network Open · doi:10.1001/jamanetworkopen.2020.9296 · Cited by 5 · cited 1×
“This caution will be especially important if progress in stem-cell technologies makes it possible to create sperm or egg cells from a person’s blood or skin cells, yielding many more embryos, noninvasively, than is possible today.(43,44)”
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Flagged first, then by citations
10 of the 46 references couldn’t be matched to a known paper.
Research works printed but not linked: 5
- 10.1016/j.cell.2019.10.033 · DOI · Paper page
- 10.1162/qjec.2010.125.2.591 · DOI
- Lou H. Eugenics then and now: constitutional limits on the use of reproductive screening technologies. Hastings Constit Law Q 2015;42:393-414 (https://repository.uchastings.edu/hastings_constitutional_law_quaterly/vol42/iss2/4/).
- 10.1111/j.1539-6053.2008.00033.x · DOI · Paper page
- 10.1257/0002828053828671 · DOI
Cited by
Sorted by citations
15 years of GWAS discovery: Realizing the promise
Abdellaoui, A., Yengo, L., Verweij, K. J. H., & Visscher, P. M. (2023) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2022.12.011 · Cited by 570
Self-citationResponsible use of polygenic risk scores in the clinic: potential benefits, risks and gaps
Polygenic Risk Score Task Force of the International Common Disease Alliance, Adeyemo, A., Balaconis, M. K., Darnes, D. R., Fatumo, S., Granados Moreno, P., Hodonsky, C. J., Inouye, M., Kanai, M., Kato, K., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01549-6 · Cited by 413
Self-citationAndreassen, O. A., Hindley, G., Frei, O., & Smeland, O. B. (2023) · World Psychiatry · doi:10.1002/wps.21034 · Cited by 284
Polygenic scores in biomedical research
Kullo, I. J., Lewis, C. M., Inouye, M., Martin, A. R., Ripatti, S., & Chatterjee, N. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-022-00470-z · Cited by 185
Self-citationMendelian imputation of parental genotypes improves estimates of direct genetic effects
Young, A. I., Nehzati, S. M., Benonisdottir, S., Okbay, A., Jayashankar, H., Lee, C., Cesarini, D., Benjamin, D. J., Turley, P., & Kong, A. (2022) · Nature Genetics · doi:10.1038/s41588-022-01085-0 · Cited by 144
Self-citation
Metadata
- Authors
- Turley, P., Meyer, M. N., Wang, N., Cesarini, D., Hammonds, E., Martin, A. R., Neale, B. M., Rehm, H. L., Wilkins-Haug, L., Benjamin, D. J., Hyman, S., Laibson, D., & Visscher, P. M.
- Affiliations
- Broad Institute (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2021-07
- Volume
- 385
- Issue
- 1
- Pages
- 78-86
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC8387884
- OpenAlex
- W3177492916
- Cited by
- 187
- References
- 46
- Citations by year
- 2026: 26 · 2025: 25 · 2024: 42 · 2023: 46 · 2022: 39 · 2021: 9
- FWCI
- 33.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Sage Foundation
- Open Philanthropy Project (010623-00001)
- Stanley Family Foundation
- Medical Research Council (1113400)
- National Health and Medical Research Council (1113400)
- National Institute on Aging (R24AG065184, R00AG062787, K99AG062787, R56AG042568, R01AG042568)
- National Institute of Mental Health (K99MH117229)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Screening and Diagnostics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Assisted Reproductive Technology and Twin Pregnancy
- Health Sciences › Medicine › Reproductive Medicine › Reproductive Health and Technologies
- Keywords
- polygenic risk score, embryo selection, in vitro fertilization, predictive power, genome-wide association study, unintended consequences, demographics, social inequality, responsible communication, reproductive technology ethics
- MeSH terms
- Educational Status, Embryo, Mammalian, Female, Fertilization in Vitro, Genetic Testing, Humans, Phenotype, Predictive Value of Tests, Pregnancy, Genetic Variation, Preimplantation Diagnosis, Multifactorial Inheritance, Genome-Wide Association Study, Gene-Environment Interaction
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