Screening Human Embryos for Polygenic Traits Has Limited Utility

Ehud Karavani, Or Zuk, Danny Zeevi, Nir Barzilai, Nikos C. Stefanis, Alex Hatzimanolis, Nikolaos Smyrnis, Dimitrios Avramopoulos, Leonid Kruglyak, Gil Atzmon, Max Lam, Todd Lencz, Shai Carmi

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1424-1435.e8
JournalCell
Volume179
Issue number6
DOIs
StatePublished - Nov 27 2019

Fingerprint

Multifactorial Inheritance
Screening
Embryonic Structures
Aptitude
Preimplantation Diagnosis
Nuclear Family
Technology

Keywords

  • cognitive ability
  • complex traits
  • embryo screening
  • embryo selection
  • height
  • polygenic scores
  • pre-implantation genetic testing
  • quantitative genetics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Karavani, E., Zuk, O., Zeevi, D., Barzilai, N., Stefanis, N. C., Hatzimanolis, A., ... Carmi, S. (2019). Screening Human Embryos for Polygenic Traits Has Limited Utility. Cell, 179(6), 1424-1435.e8. https://doi.org/10.1016/j.cell.2019.10.033

Screening Human Embryos for Polygenic Traits Has Limited Utility. / Karavani, Ehud; Zuk, Or; Zeevi, Danny; Barzilai, Nir; Stefanis, Nikos C.; Hatzimanolis, Alex; Smyrnis, Nikolaos; Avramopoulos, Dimitrios; Kruglyak, Leonid; Atzmon, Gil; Lam, Max; Lencz, Todd; Carmi, Shai.

In: Cell, Vol. 179, No. 6, 27.11.2019, p. 1424-1435.e8.

Research output: Contribution to journalArticle

Karavani, E, Zuk, O, Zeevi, D, Barzilai, N, Stefanis, NC, Hatzimanolis, A, Smyrnis, N, Avramopoulos, D, Kruglyak, L, Atzmon, G, Lam, M, Lencz, T & Carmi, S 2019, 'Screening Human Embryos for Polygenic Traits Has Limited Utility', Cell, vol. 179, no. 6, pp. 1424-1435.e8. https://doi.org/10.1016/j.cell.2019.10.033
Karavani E, Zuk O, Zeevi D, Barzilai N, Stefanis NC, Hatzimanolis A et al. Screening Human Embryos for Polygenic Traits Has Limited Utility. Cell. 2019 Nov 27;179(6):1424-1435.e8. https://doi.org/10.1016/j.cell.2019.10.033
Karavani, Ehud ; Zuk, Or ; Zeevi, Danny ; Barzilai, Nir ; Stefanis, Nikos C. ; Hatzimanolis, Alex ; Smyrnis, Nikolaos ; Avramopoulos, Dimitrios ; Kruglyak, Leonid ; Atzmon, Gil ; Lam, Max ; Lencz, Todd ; Carmi, Shai. / Screening Human Embryos for Polygenic Traits Has Limited Utility. In: Cell. 2019 ; Vol. 179, No. 6. pp. 1424-1435.e8.
@article{01d3d8bc0b2e41b280951da153513d38,
title = "Screening Human Embryos for Polygenic Traits Has Limited Utility",
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.",
keywords = "cognitive ability, complex traits, embryo screening, embryo selection, height, polygenic scores, pre-implantation genetic testing, quantitative genetics",
author = "Ehud Karavani and Or Zuk and Danny Zeevi and Nir Barzilai and Stefanis, {Nikos C.} and Alex Hatzimanolis and Nikolaos Smyrnis and Dimitrios Avramopoulos and Leonid Kruglyak and Gil Atzmon and Max Lam and Todd Lencz and Shai Carmi",
year = "2019",
month = "11",
day = "27",
doi = "10.1016/j.cell.2019.10.033",
language = "English (US)",
volume = "179",
pages = "1424--1435.e8",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "6",

}

TY - JOUR

T1 - Screening Human Embryos for Polygenic Traits Has Limited Utility

AU - Karavani, Ehud

AU - Zuk, Or

AU - Zeevi, Danny

AU - Barzilai, Nir

AU - Stefanis, Nikos C.

AU - Hatzimanolis, Alex

AU - Smyrnis, Nikolaos

AU - Avramopoulos, Dimitrios

AU - Kruglyak, Leonid

AU - Atzmon, Gil

AU - Lam, Max

AU - Lencz, Todd

AU - Carmi, Shai

PY - 2019/11/27

Y1 - 2019/11/27

N2 - 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.

AB - 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.

KW - cognitive ability

KW - complex traits

KW - embryo screening

KW - embryo selection

KW - height

KW - polygenic scores

KW - pre-implantation genetic testing

KW - quantitative genetics

UR - http://www.scopus.com/inward/record.url?scp=85075537048&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85075537048&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2019.10.033

DO - 10.1016/j.cell.2019.10.033

M3 - Article

C2 - 31761530

AN - SCOPUS:85075537048

VL - 179

SP - 1424-1435.e8

JO - Cell

JF - Cell

SN - 0092-8674

IS - 6

ER -