Whole-genome risk prediction of common diseases in human preimplantation embryos.
Nat Med
; 28(3): 513-516, 2022 03.
Article
em En
| MEDLINE
| ID: mdl-35314819
ABSTRACT
Preimplantation genetic testing (PGT) of in-vitro-fertilized embryos has been proposed as a method to reduce transmission of common disease; however, more comprehensive embryo genetic assessment, combining the effects of common variants and rare variants, remains unavailable. Here, we used a combination of molecular and statistical techniques to reliably infer inherited genome sequence in 110 embryos and model susceptibility across 12 common conditions. We observed a genotype accuracy of 99.0-99.4% at sites relevant to polygenic risk scoring in cases from day-5 embryo biopsies and 97.2-99.1% in cases from day-3 embryo biopsies. Combining rare variants with polygenic risk score (PRS) magnifies predicted differences across sibling embryos. For example, in a couple with a pathogenic BRCA1 variant, we predicted a 15-fold difference in odds ratio (OR) across siblings when combining versus a 4.5-fold or 3-fold difference with BRCA1 or PRS alone. Our findings may inform the discussion of utility and implementation of genome-based PGT in clinical practice.
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1
Base de dados:
MEDLINE
Assunto principal:
Diagnóstico Pré-Implantação
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article