Problems with Using Polygenic Scores to Select Embryos

“When polygenic scores constructed from such studies have been tested on participants who were not of European ancestries, their predictive power was much lower.(10) Figure 1 shows the expected differences in educational attainment between the person with the highest polygenic score among 10 persons and a person select…”

“The authors of a recent paper reported that according to current polygenic scoring for educational attainment, the prevalence of college completion is roughly 10% among persons in the lowest quintile and roughly 45 to 60% among those in the highest quintile.(6) Drawing on these differences, advocates have encouraged p…”

“Second, a sizeable portion of the predictive power of the polygenic score for persons from different families comes from “gene–environment correlation” — that is, persons with high polygenic scores are likely to be raised in family environments that promote educational attainment.(9) For example, such persons are like…”

“One particularly relevant misconception is “genetic determinism”: potential customers may expect that ESPS guarantees the outcome they want.(12) Furthermore, people tend to neglect variance,(13) and polygenic scores do not capture all sources of genetic variation.”

“org July 1, 2021 85 tion would have a greater effect than many environmental interventions that have been implemented.(45) It seems plausible that some patients who have undergone IVF will find ESPS attractive — more so as the expected gains increase.”

“First, PRS-based embryo scores provide only a relative ranking within the limited cohort of available sibling embryos, rather than an absolute diagnostic prediction [100,101].”

“…can yield viable ongoing pregnancies (102), introducing additional complexity that future non-invasive AI ploidy models will need to incorporate; the parallel extension of embryo screening to polygenic risk raises distinct scienti fi c and ethical questions that remain unresolved (103 – 105).”

“Second, case–control PRSs explain less than 8% of the variance in risk of SCZ in the population 8 (6–13% using PRS-CS 5 ; Supplementary Table 23), 15.”

“All previous models for PES outcomes (Treff et al. 2019a, Turley et al. 2021, Lencz et al. 2021, Moore et al. 2025) reported risk reductions versus the number of (euploid) embryos being screened, implicitly assuming that the transferred embryo will be born.”

“Although the integration of PGIs in IVF is controversial, there is the chance that PGI could become normalized in this setting and then utilized in further segments of society (Canter et al. 2023).”

“To simulate the risk of embryos, we used the liability threshold model (LTM) 41 , which is commonly utilized in genetic modeling (including PES 42–44 ) and empirical studies of real-world populations 45 .”

“Other concerns include societal misinterpretation of risk perception (i.e., absolute vs. relative risk) as well as the technology having limited availability for patients of certain ethnicities [1].”

“Recently, selection of embryos during IVF treatments has been advocated to bring genetic inheritances under some control (Turley et al., 2021).”

“PGT existe desde hace años para el estudio de patología cromosómica (PGT-A, por aneuploidías) y monogénica (PGT-M), y en la actualidad hay disponibilidad emergente del estudio de condiciones poligénicas (PGT-P) (Treff et al. , 2020; Turley et al. , 2021).”

“Others have gone a step 455 further and advocated using PGS to screen embryos for cognitive traits [66], a position that has 456 received well-warranted criticism [67, 68].”

“PRS quantifies one’s predisposition to develop a particular condition or trait and are derived from genome wide association studies (GWAS) (Turley et al. 2021).”

“Equating polygenic scores with prediction amounts to the implicit promotion of a false genetic determinism, while leaving aside the problems of pleiotropy, complexity and inequity they acknowledge (Turley et al. 2021).”

“The recent emergence of commercial GRS use for human embryo selection following in vitro fertilization is problematic for multiple reasons, not the least of which are ethical concerns related to selection based on inadequately characterized probabilities of more or less desirable adult traits(4).”