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

Cell. 2019 Nov 27;179(6):1424-1435.e8. doi: 10.1016/j.cell.2019.10.033. Epub 2019 Nov 21.

Authors

Ehud Karavani¹, Or Zuk², Danny Zeevi³, Nir Barzilai⁴, Nikos C Stefanis⁵, Alex Hatzimanolis⁶, Nikolaos Smyrnis⁷, Dimitrios Avramopoulos⁸, Leonid Kruglyak⁹, Gil Atzmon¹⁰, Max Lam¹¹, Todd Lencz¹², Shai Carmi¹³

Affiliations

¹ Braun School of Public Health and Community Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
² Department of Statistics, The Hebrew University of Jerusalem, Jerusalem 9190501, Israel.
³ Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁴ Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Genetics, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
⁵ Department of Psychiatry, National and Kapodistrian University of Athens Medical School, Eginition Hospital, 115 28 Athens, Greece; University Mental Health Research Institute, 115 27 Athens, Greece; Neurobiology Research Institute, Theodor-Theohari Cozzika Foundation, 115 21 Athens, Greece.
⁶ Department of Psychiatry, National and Kapodistrian University of Athens Medical School, Eginition Hospital, 115 28 Athens, Greece; Neurobiology Research Institute, Theodor-Theohari Cozzika Foundation, 115 21 Athens, Greece.
⁷ Department of Psychiatry, National and Kapodistrian University of Athens Medical School, Eginition Hospital, 115 28 Athens, Greece; University Mental Health Research Institute, 115 27 Athens, Greece.
⁸ Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁹ Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
¹⁰ Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Genetics, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Biology, Faculty of Natural Sciences, University of Haifa, Haifa 3498838, Israel.
¹¹ Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY 11004, USA; Institute of Behavioral Science, Feinstein Institutes of Medical Research, Manhasset, NY 11030, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
¹² Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY 11004, USA; Institute of Behavioral Science, Feinstein Institutes of Medical Research, Manhasset, NY 11030, USA; Department of Psychiatry, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11549, USA. Electronic address: [email protected].
¹³ Braun School of Public Health and Community Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel. Electronic address: [email protected].

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adult
Embryo, Mammalian / metabolism*
Family
Genetic Testing*
Genome-Wide Association Study
Humans
Multifactorial Inheritance / genetics*
Phenotype

Abstract

Publication types

MeSH terms

Grants and funding