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Cited by 111Prenatal Screening and DiagnosticsAssisted Reproductive Technology and Twin PregnancyGenetic Associations and Epidemiology

Screening Human Embryos for Polygenic Traits Has Limited Utility

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Karavani, Ehud, Zuk, Or, Zeevi, Danny, Barzilai, Nir, Stefanis, Nikos C., Hatzimanolis, Alex, Smyrnis, Nikolaos, Avramopoulos, Dimitrios +5 more·2019·Cell
DOI 10.1016/j.cell.2019.10.033PMC PMC6957074

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Abstract

The increasing proportion of variance in human complex traits explained by polygenic scores, along with progress in preimplantation genetic diagnosis, suggests the possibility of screening embryos for traits such as height or cognitive ability. However, the expected outcomes of embryo screening are unclear, which undermines discussion of associated ethical concerns. Here, we use theory, simulations, and real data to evaluate the potential gain of embryo screening, defined as the difference in trait value between the top-scoring embryo and the average embryo. The gain increases very slowly with the number of embryos but more rapidly with the variance explained by the score. Given current technology, the average gain due to screening would be ≈2.5 cm for height and ≈2.5 IQ points for cognitive ability. These mean values are accompanied by wide prediction intervals, and indeed, in large nuclear families, the majority of children top-scoring for height are not the tallest.

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  • Our results do not support any immediate medical or clinical applications, such as polygenic prediction in direct-to-consumer services.

    “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 [50]

    The Discussion says limitations in polygenic-score accuracy and other constraints reduce the utility of embryo screening. It does not extend that conclusion to all immediate medical or clinical applications, or evaluate polygenic prediction in direct-to-consumer services generally; its mention of consumers concerns embryo selection specifically. The claim therefore applies the paper's narrower finding too broadly. (LLM, conf=0.83)

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Authors
Karavani, E., Zuk, O., Zeevi, D., Barzilai, N., Stefanis, N. C., Hatzimanolis, A., Smyrnis, N., Avramopoulos, D., Kruglyak, L., Atzmon, G., Lam, M., Lencz, T., & Carmi, S.
Affiliations
  • Hebrew University of Jerusalem (IL)
  • University of California, Los Angeles (US)
  • Albert Einstein College of Medicine (US)
  • National and Kapodistrian University of Athens (GR)
  • Johns Hopkins University (US)
  • Howard Hughes Medical Institute (US)
  • Broad Institute (US)
  • Feinstein Institute for Medical Research (US)
Corresponding author
  • Lencz, Todd
  • Carmi, Shai
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2019-11
Volume
179
Issue
6
Pages
1424-1435.e8
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2019.10.033
PMC
PMC6957074
OpenAlex
W2990673704
Cited by
111
References
129
Citations by year
2026: 15 · 2025: 13 · 2024: 15 · 2023: 18 · 2022: 22 · 2021: 18 · 2020: 9 · 2019: 1
FWCI
13.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • James S. McDonnell Foundation
  • Abisch-Frenkel-Stiftung
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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
embryo screening, polygenic risk score, preimplantation genetic diagnosis, complex traits, height, cognitive ability, prediction intervals, prediction accuracy, reproductive ethics
MeSH terms
Adult, Embryo, Mammalian, Family, Genetic Testing, Humans, Phenotype, Multifactorial Inheritance, Genome-Wide Association Study

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