Evaluating concordance of preimplantation genetic testing-whole-genome sequencing with genetic findings in live-born children.
- 1Laboratory Department, Orchid Health, Durham, North Carolina.
- 2Marin Fertility Center, Greenbrae, California.
Abstract
Objective
To clinically assess concordance between preimplantation genetic testing-whole-genome sequencing (PGT-WGS) and whole-genome sequencing results from corresponding live-born children, including evaluation of genome-wide variants, targeted gene panels, de novo variants, and genetic risk scores.Design
Patients underwent a standard in vitro fertilization workflow with PGT-WGS. After pregnancy or live birth, patients were contacted for consent to participate in this study. This small study included 10 biopsy-child pairs. Deoxyribonucleic acid (DNA) samples were collected from children, and whole-genome sequencing was performed accordingly. Genetic findings from PGT-WGS were compared with the child's whole-genome sequencing results. For de novo variant assessment (3 biopsy-child pairs), parental samples were also requested.Subjects
Clinical trophectoderm biopsy samples, corresponding live-born children, and parental DNA samples.Exposure
No applicable.Main outcome measures
Variant concordance across the whole genome and within designated gene panels; concordance of clinically relevant variants and de novo variants; concordance of functionally significant single-nucleotide polymorphisms (SNPs), including HLA and APOE; and resulting genetic risk scores.Results
Analysis of single-nucleotide variants (SNVs) and insertions/deletions (indels) identified an average of 3,562,534 variants genome-wide and 2,656 variants within the 1,200-gene panel per embryo-child pair, yielding a sensitivity of 97.6% and a precision of 98.4% on genome and 98.4% and 98.7% respectively, on monogenic panels.Traditional PGT approaches do not enable prospective screening for de novo variants. In this study, all 42 confirmed de novo variants detected in live-born children were also identified in the corresponding PGT-WGS results. High concordance (>99%) was observed on HLA, APOE, as well as SNPs used for genetic risk scores.Conclusion
This study provides a small clinical study comparing PGT-WGS results with whole-genome sequencing findings in live-born children. Preimplantation genetic testing-whole-genome sequencing, offered using an opt-in panel of approximately 1,200 genes, demonstrated high sensitivity and precision and enabled direct interrogation of the trophectoderm genome. It has the feasibility to identify de novo variants.
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BibTeX
@article{li2026evaluating,
title = {{Evaluating concordance of preimplantation genetic testing-whole-genome sequencing with genetic findings in live-born children.}},
author = {Shenglai Li and Benjamin Podgursky and Maria Katz and Maxwell Silver and Thomas Giardina and Adriana Brown and Nicholas Schuch and Qinnan Zhang and Peter Uzelac and Noor Siddiqui and Yuntao Xia},
journal = {F\&S reports},
year = {2026},
month = aug,
doi = {10.1016/j.xfre.2026.08.002},
url = {https://europepmc.org/article/MED/42903677},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Evaluating concordance of preimplantation genetic testing-whole-genome sequencing with genetic findings in live-born children.
AU - Shenglai Li
AU - Benjamin Podgursky
AU - Maria Katz
AU - Maxwell Silver
AU - Thomas Giardina
AU - Adriana Brown
AU - Nicholas Schuch
AU - Qinnan Zhang
AU - Peter Uzelac
AU - Noor Siddiqui
AU - Yuntao Xia
PY - 2026
DA - 2026/08/18
JO - F&S reports
DO - 10.1016/j.xfre.2026.08.002
UR - https://europepmc.org/article/MED/42903677
AB - Objective To clinically assess concordance between preimplantation genetic testing-whole-genome sequencing (PGT-WGS) and whole-genome sequencing results from corresponding live-born children, including evaluation of genome-wide variants, targeted gene panels, de novo variants, and genetic risk scores.Design Patients underwent a standard in vitro fertilization workflow with PGT-WGS. After pregnancy or live birth, patients were contacted for consent to participate in this study. This small study included 10 biopsy-child pairs. Deoxyribonucleic acid (DNA) samples were collected from children, and whole-genome sequencing was performed accordingly. Genetic findings from PGT-WGS were compared with the child's whole-genome sequencing results. For de novo variant assessment (3 biopsy-child pairs), parental samples were also requested.Subjects Clinical trophectoderm biopsy samples, corresponding live-born children, and parental DNA samples.Exposure No applicable.Main outcome measures Variant concordance across the whole genome and within designated gene panels; concordance of clinically relevant variants and de novo variants; concordance of functionally significant single-nucleotide polymorphisms (SNPs), including HLA and APOE; and resulting genetic risk scores.Results Analysis of single-nucleotide variants (SNVs) and insertions/deletions (indels) identified an average of 3,562,534 variants genome-wide and 2,656 variants within the 1,200-gene panel per embryo-child pair, yielding a sensitivity of 97.6% and a precision of 98.4% on genome and 98.4% and 98.7% respectively, on monogenic panels.Traditional PGT approaches do not enable prospective screening for de novo variants. In this study, all 42 confirmed de novo variants detected in live-born children were also identified in the corresponding PGT-WGS results. High concordance (>99%) was observed on HLA, APOE, as well as SNPs used for genetic risk scores.Conclusion This study provides a small clinical study comparing PGT-WGS results with whole-genome sequencing findings in live-born children. Preimplantation genetic testing-whole-genome sequencing, offered using an opt-in panel of approximately 1,200 genes, demonstrated high sensitivity and precision and enabled direct interrogation of the trophectoderm genome. It has the feasibility to identify de novo variants.
SN - 2666-3341
ER -