{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T20:55:39Z","timestamp":1784753739954,"version":"3.55.0"},"reference-count":119,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T00:00:00Z","timestamp":1633996800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T00:00:00Z","timestamp":1633996800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T00:00:00Z","timestamp":1633996800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HG011711"],"award-info":[{"award-number":["R01HG011711"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Polygenic risk scores (PRSs) have been offered since 2019 to screen in vitro fertilization embryos for genetic liability to adult diseases, despite a lack of comprehensive modeling of expected outcomes. Here we predict, based on the liability threshold model, the expected reduction in complex disease risk following\n                    <jats:italic>polygenic embryo screening<\/jats:italic>\n                    for a single disease. A strong determinant of the potential utility of such screening is the\n                    <jats:italic>selection strategy<\/jats:italic>\n                    , a factor that has not been previously studied. When only embryos with a very high PRS are excluded, the achieved risk reduction is minimal. In contrast, selecting the embryo with the lowest PRS can lead to substantial relative risk reductions, given a sufficient number of viable embryos. We systematically examine the impact of several factors on the utility of screening, including: variance explained by the PRS, number of embryos, disease prevalence, parental PRSs, and parental disease status. We consider both relative and absolute risk reductions, as well as population-averaged and per-couple risk reductions, and also examine the risk of pleiotropic effects. Finally, we confirm our theoretical predictions by simulating \u2018virtual\u2019 couples and offspring based on real genomes from schizophrenia and Crohn\u2019s disease case-control studies. We discuss the assumptions and limitations of our model, as well as the potential emerging ethical concerns.\n                  <\/jats:p>","DOI":"10.7554\/elife.64716","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T20:44:11Z","timestamp":1633985051000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.64716","source":"Crossref","is-referenced-by-count":66,"title":["Utility of polygenic embryo screening for disease depends on the selection strategy"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8586-338X","authenticated-orcid":true,"given":"Todd","family":"Lencz","sequence":"first","affiliation":[{"name":"Departments of Psychiatry and Molecular Medicine, Zucker School of Medicine at Hofstra\/Northwell, Hempstead, United States"},{"name":"Department of Psychiatry, Division of Research, The Zucker Hillside Hospital Division of Northwell Health, Glen Oaks, United States"},{"name":"Institute for Behavioral Science, The Feinstein Institutes for Medical Research, Manhasset, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Backenroth","sequence":"additional","affiliation":[{"name":"Braun School of Public Health and Community Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Einat","family":"Granot-Hershkovitz","sequence":"additional","affiliation":[{"name":"Braun School of Public Health and Community Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Green","sequence":"additional","affiliation":[{"name":"Braun School of Public Health and Community Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle","family":"Gettler","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7959-0466","authenticated-orcid":true,"given":"Judy H","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, United States"},{"name":"The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, United States"},{"name":"Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omer","family":"Weissbrod","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Harvard T.H. 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