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

doi:10.1016/j.cell.2019.10.033

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

54 Scopus citations

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 language	American English
Pages (from-to)	1424-1435.e8
Journal	Cell
Volume	179
Issue number	6
DOIs	https://doi.org/10.1016/j.cell.2019.10.033
State	Published - 27 Nov 2019

Bibliographical note

Funding Information:
We thank Yaniv Erlich and Peter Visscher for discussions. S.C. thanks the Abisch-Frenkel Foundation for financial support. We thank the NIH (GM112625) for supporting the CGSI workshop in which one of the collaborations was initiated. T.L. and M.L. were supported, in part, by a grant from the NIH (R01MH117646). The study of the nuclear families was supported by the James S. McDonnell Centennial Fellowship in Human Genetics to L.K. Conceptualization, T.L. and S.C.; Methodology, O.Z. T.L. and S.C.; Investigation, E.K. O.Z. D.Z. T.L. and S.C.; Resources, N.B. N.C.S. A.H. N.S. D.A. L.K. and G.A.; Formal Analysis, E.K. and S.C.; Data Curation, D.Z. and M.L.; Writing – Original Draft, E.K. O.Z. T.L. and S.C.; Writing – Review & Editing, E.K. O.Z. D.Z. N.B. L.K. G.A. T.L. and S.C.; Visualization, E.K. and S.C.; Funding Acquisition, T.L. and S.C.; Supervision, T.L. and S.C. The authors declare no competing interests.

Funding Information:
We thank Yaniv Erlich and Peter Visscher for discussions. S.C. thanks the Abisch-Frenkel Foundation for financial support. We thank the NIH ( GM112625 ) for supporting the CGSI workshop in which one of the collaborations was initiated. T.L. and M.L. were supported, in part, by a grant from the NIH ( R01MH117646 ). The study of the nuclear families was supported by the James S. McDonnell Centennial Fellowship in Human Genetics to L.K.

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

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

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10.1016/j.cell.2019.10.033

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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",

note = "Funding Information: We thank Yaniv Erlich and Peter Visscher for discussions. S.C. thanks the Abisch-Frenkel Foundation for financial support. We thank the NIH (GM112625) for supporting the CGSI workshop in which one of the collaborations was initiated. T.L. and M.L. were supported, in part, by a grant from the NIH (R01MH117646). The study of the nuclear families was supported by the James S. McDonnell Centennial Fellowship in Human Genetics to L.K. Conceptualization, T.L. and S.C.; Methodology, O.Z. T.L. and S.C.; Investigation, E.K. O.Z. D.Z. T.L. and S.C.; Resources, N.B. N.C.S. A.H. N.S. D.A. L.K. and G.A.; Formal Analysis, E.K. and S.C.; Data Curation, D.Z. and M.L.; Writing – Original Draft, E.K. O.Z. T.L. and S.C.; Writing – Review & Editing, E.K. O.Z. D.Z. N.B. L.K. G.A. T.L. and S.C.; Visualization, E.K. and S.C.; Funding Acquisition, T.L. and S.C.; Supervision, T.L. and S.C. The authors declare no competing interests. Funding Information: We thank Yaniv Erlich and Peter Visscher for discussions. S.C. thanks the Abisch-Frenkel Foundation for financial support. We thank the NIH ( GM112625 ) for supporting the CGSI workshop in which one of the collaborations was initiated. T.L. and M.L. were supported, in part, by a grant from the NIH ( R01MH117646 ). The study of the nuclear families was supported by the James S. McDonnell Centennial Fellowship in Human Genetics to L.K. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

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doi = "10.1016/j.cell.2019.10.033",

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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

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PY - 2019/11/27

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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.

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KW - height

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KW - pre-implantation genetic testing

KW - quantitative genetics

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ER -

Screening Human Embryos for Polygenic Traits Has Limited Utility

Abstract

Bibliographical note

Keywords

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