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PEStimate: predicting offspring disease risk after polygenic embryo screening
Liraz Klausner1, Ateret Revital1, Todd Lencz2,3,4,5
1Braun School of Public Health and Community Medicine, The Hebrew University of Jerusalem, Jerusalem, 9112102, Israel.
Insights
Polygenic embryo screening (PES) can estimate offspring disease risk, but previous models overestimated benefits. A new tool, PEStimate, accounts for implantation failure, providing more accurate predictions for polygenic risk assessment.
Area of Science:
- Genetics
- Reproductive Medicine
- Bioinformatics
Background:
- Polygenic embryo screening (PES) is a novel technology for assessing genetic risk of complex diseases in IVF embryos.
- Current PES models often rely on epidemiological predictions and may not account for all factors influencing outcomes.
- Previous models have not incorporated the possibility of embryo implantation failure, potentially leading to overestimated risk reductions.
Purpose of the Study:
- To develop and present PEStimate, a user-friendly online application for predicting the outcomes of polygenic embryo screening for single-gene disorders.
- To provide a tool that allows for a more accurate estimation of risk reduction by incorporating embryo implantation failure.
- To enable stakeholders to better evaluate the potential benefits and harms of PES.
Main Methods:
- Development of an online application, PEStimate, accessible via a web link.
- Implementation of a model that predicts offspring risk with and without PES, considering various user-adjustable parameters.
- Inclusion of embryo implantation failure as a novel factor in the risk prediction model.
Main Results:
- PEStimate generates predictions of offspring disease risk and visualizes risk reduction across different parameters.
- The model demonstrates that previous risk reduction estimates for PES may have been overestimated due to the exclusion of implantation failure.
- The tool allows customization based on factors like embryo availability, live birth rates, disease prevalence, and parental genetic information.
Conclusions:
- PEStimate offers a more realistic assessment of polygenic embryo screening outcomes by incorporating embryo implantation failure.
- This tool is valuable for geneticists, healthcare professionals, and patients in understanding the impact of PES.
- The application facilitates informed decision-making regarding the use of PES by weighing potential benefits against societal and personal harms.
Motivation:
Polygenic embryo screening (PES) is a new, controversial technology, whereby human in vitro fertilization embryos are screened for their genetic risk of complex, polygenic diseases. PES aims to reduce the disease burden in offspring by prioritizing the selection of low-risk embryos. However, given that polygenic diseases are usually late-onset, PES outcomes must be estimated by epidemiological modeling. The liability threshold model has been previously used to predict outcomes. However, predictions rely on complex sets of equations, some of which require numerical integration or simulation. Further, previous models failed to account for the possibility that the selected embryo will not be born.
Results:
Here, we present PEStimate, a freely available online app for predicting PES outcomes when screening for a single disease. PEStimate predicts the offspring risk with and without PES, as well as generates plots of the risk reduction versus key parameters. Users can adjust the number of available embryos, the live birth rate, the disease prevalence, the accuracy of the genetic risk predictor, the embryo selection method, the genetic risk of parents, and the disease status of parents, siblings, uncles/aunts, and grandparents of the embryos. Our model includes, for the first time, the possibility of embryo implantation failure, showing that risk reductions have been previously overestimated. PEStimate provides geneticists, healthcare professionals, patients, and other stakeholders with a necessary tool for examining the impact of PES and weighing its potential benefits against possible personal and societal harms.
Availability And Implementation:
PEStimate: https://polygenicembryo.shinyapps.io/pestimate. Source code: https://github.com/Lirazk/PEStimate.
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