O-226 Is there a place for polygenic risk scoring in PGT (PGT-P)?

Abstract

Abstract Preimplantation genetic testing (PGT), by embryo biopsy and genetic testing for inherited diseases and chromosome abnormalities following IVF, is now well established world-wide. PGT for monogenic conditions (PGT-M) is generally performed for childhood-onset, lethal disorders, but is increasingly accepted for certain adult-onset conditions, conditions with available treatment options or conditions with lower penetrance. Over recent years, machine learning methods applied to large genomic datasets, including genome-wide association studies (GWAS) using single nucleotide polymorphism (SNP) genotyping, has enabled polygenic risk scores (PRSs) to be calculated to identify individuals who are at elevated risk for a broad range of conditions including important common multifactorial diseases, such as coronary artery disease (CAD), diabetes, hypertension and various cancers. It is now possible to perform genome-wide SNP genotyping of embryo biopsy samples with the same accuracy as adult genomic DNA and the first live birth following PGT for polygenic risk scoring (PGT-P) was reported in 2019 (Treff et al (2019) Front Endocrinol 10, 845) . The clinical application of PGT-P is controversial and raises many practical, ethical and societal issues. To examine the question ‘is there a place for PRS in PGT’, the example of predisposition to breast cancer will be reviewed.