Embryo Screening for Polygenic Disease Risk: Recent Advances and Ethical Considerations

Machine learning methods applied to large genomic datasets (such as those used in GWAS) have led to the creation of polygenic risk scores (PRSs) that can be used identify individuals who are at highly elevated risk for important disease conditions, such as coronary artery disease (CAD), diabetes, hypertension, breast cancer, and many more. PRSs have been validated in large population groups across multiple continents and are under evaluation for widespread clinical use in adult health. It has been shown that PRSs can be used to identify which of two individuals is at a lower disease risk, even when these two individuals are siblings from a shared family environment. The relative risk reduction (RRR) from choosing an embryo with a lower PRS (with respect to one chosen at random) can be quantified by using these sibling results. New technology for precise embryo genotyping allows more sophisticated preimplantation ranking with better results than the current method of selection that is based on morphology. We review the advances described above and discuss related ethical considerations.

Automated summary

Machine learning applied to large genomic datasets has led to the creation of polygenic risk scores (PRSs) for identifying individuals at high risk for important diseases. These scores have been validated in global populations and are being evaluated for clinical use in adult health. PRSs can differentiate between low-risk individuals, and new technology allows for more precise embryo genotyping for improved preimplantation selection.