Polygenic Risk Scores, Embryo Selection and the Evidentiary Gap
G. Owen Schaefer1, Centre for Biomedical Ethics, Yong Loo Lin School of Medicine, National University of Singapore 1Centre for Biomedical Ethics, Yong Loo Lin School of Medicine, National University of Singapore
Abstract
Polygenic Risk Scores, Embryo Selection and the Evidentiary Gap
By G. Owen Schaefer, See Tow Hui Xin and Julian Savulescu
Recent work in genetics has shifted emphasis away from monogenic traits towards polygenic effects on phenotypes, with a proliferation of ‘polygenic risk scores’ (PRSs). PRSs purport to estimate an individual’s likelihood of developing a certain condition, trait or outcome based on multiple genetic markers, better reflecting the polygenic underpinnings of genetics. Some have further suggested applying PRSs to embryo selection, soas to improve on the health of resultant children compared with traditional monogenic approaches to preimplantation genetic selection.
One difficulty with this application of PRSs is their limited evidence base. Among various shortcomings, PRSs are typically generated based on particular genomic datasets (typically Western) whose results may not generalize to other populations. How, then, should under-studied populations approach the application of PRSs to embryo selection? This poses something of a dilemma: either proceed with PRS-based embryo selection based on potentially flawed data, undermining both safety and efficacy of the intervention; or, devote resources to validate PRSs locally, potentially redirecting substantial resources to questions of arguably low social priority.
We argue that, in absence of locally validated PRSs, application to embryo selection is premature. To some extent, this may be a temporary problem, as local PRS research may have social utility (and hence funding justification) outside of embryo selection applications. It also suggests a place where research should potentially be led by private industry rather than the public, in order to avoid misdirecting valuable public funds.
Biography
G. Owen Schaefer is an Assistant Professor at the Centre for Biomedical Ethics, Yong Loo Lin School of Medicine, National University of Singapore. He received his DPhil in Philosophy from Oxford University, and has completed fellowships at the National Institutes of Health’s Department of Bioethics and the Oxford Centre for Neuroethics. His primary interests lie in the ethics of developing novel biomedical technologies. He has written on big data, research ethics, gene editing, human enhancement, precision medicine, vaccine allocation, assisted reproduction and in vitro meat.