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Screening human embryos for polygenic traits has limited utility

Ehud Karavani, Or Zuk, Danny Zeevi, Gil Atzmon, Nir Barzilai, Nikos C. Stefanis, Alex Hatzimanolis, Nikolaos Smyrnis, Dimitrios Avramopoulos, Leonid Kruglyak, Max Lam, Todd Lencz, Shai Carmi
doi: https://doi.org/10.1101/626846
Ehud Karavani
1Braun School of Public Health and Community Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
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Or Zuk
2Department of Statistics, The Hebrew University of Jerusalem, Jerusalem, Israel
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Danny Zeevi
3Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA
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Gil Atzmon
4Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA
5Department of Genetics, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, USA
6Department of Biology, Faculty of Natural Science, University of Haifa, Haifa, Israel
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Nir Barzilai
4Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA
5Department of Genetics, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, USA
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Nikos C. Stefanis
7Department of Psychiatry, National and Kapodistrian University of Athens Medical School, Eginition Hospital, Athens, Greece
8University Mental Health Research Institute, Athens, Greece
9Neurobiology Research Institute, Theodor-Theohari Cozzika Foundation, Athens, Greece
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Alex Hatzimanolis
7Department of Psychiatry, National and Kapodistrian University of Athens Medical School, Eginition Hospital, Athens, Greece
8University Mental Health Research Institute, Athens, Greece
9Neurobiology Research Institute, Theodor-Theohari Cozzika Foundation, Athens, Greece
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Nikolaos Smyrnis
7Department of Psychiatry, National and Kapodistrian University of Athens Medical School, Eginition Hospital, Athens, Greece
8University Mental Health Research Institute, Athens, Greece
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Dimitrios Avramopoulos
10Department of Psychiatry, Johns Hopkins University School of Medicine, MD, Baltimore, USA
11McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Leonid Kruglyak
3Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA
12Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA, USA
13Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA, USA
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Max Lam
14Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, USA
15Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA
16Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA
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Todd Lencz
14Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, USA
15Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA
17Department of Psychiatry, Hofstra Northwell School of Medicine, Hempstead, NY, USA
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  • For correspondence: shai.carmi@huji.ac.il tlencz@northwell.edu
Shai Carmi
1Braun School of Public Health and Community Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
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  • For correspondence: shai.carmi@huji.ac.il tlencz@northwell.edu
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Abstract

Genome-wide association studies have led to the development of polygenic score (PS) predictors that explain increasing proportions of the variance in human complex traits. In parallel, progress in preimplantation genetic testing now allows genome-wide genotyping of embryos generated via in vitro fertilization (IVF). Jointly, these developments suggest the possibility of screening embryos for polygenic traits such as height or cognitive function. There are clear ethical, legal, and societal concerns regarding such a procedure, but these cannot be properly discussed in the absence of data on the expected outcomes of screening. Here, we use theory, simulations, and real data to evaluate the potential gain of PS-based embryo selection, defined as the expected difference in trait value between the top-scoring embryo and an average, unselected embryo. We observe that the gain increases very slowly with the number of embryos, but more rapidly with increased variance explained by the PS. Given currently available polygenic predictors and typical IVF yields, the average gain due to selection would be ≈2.5cm if selecting for height, and ≈2.5 IQ (intelligence quotient) points if selecting for cognitive function. These mean values are accompanied by wide confidence intervals; in real data drawn from nuclear families with up to 20 offspring each, we observe that the offspring with the highest PS for height was the tallest only in 25% of the families. We discuss prospects and limitations of PS-based embryo selection for the foreseeable future.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted May 05, 2019.
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Screening human embryos for polygenic traits has limited utility
Ehud Karavani, Or Zuk, Danny Zeevi, Gil Atzmon, Nir Barzilai, Nikos C. Stefanis, Alex Hatzimanolis, Nikolaos Smyrnis, Dimitrios Avramopoulos, Leonid Kruglyak, Max Lam, Todd Lencz, Shai Carmi
bioRxiv 626846; doi: https://doi.org/10.1101/626846
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Screening human embryos for polygenic traits has limited utility
Ehud Karavani, Or Zuk, Danny Zeevi, Gil Atzmon, Nir Barzilai, Nikos C. Stefanis, Alex Hatzimanolis, Nikolaos Smyrnis, Dimitrios Avramopoulos, Leonid Kruglyak, Max Lam, Todd Lencz, Shai Carmi
bioRxiv 626846; doi: https://doi.org/10.1101/626846

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