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Utilizing non-invasive prenatal test sequencing data for human genetic investigation

Authors: Siyang Liu,Yanhong Liu,Yuqin Gu,Xingchen Lin,Huanhuan Zhu,Hankui Liu,Zhe Xu,Shiyao Cheng,Xianmei Lan,Linxuan Li,Mingxi Huang,Hao Li,Rasmus Nielsen,Robert W. Davies,Anders Albrechtsen,Guo-Bo Chen,Xiu Qiu,Xin Jin,Shujia Huang
Journal: Cell Genomics
Publisher: Elsevier BV
Publish date: 2024-10
ISSN: 2666-979X DOI: 10.1016/j.xgen.2024.100669
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The entire study is predicated on the claim that NIPT data, which is a mixture of ~90% maternal and ~10% fetal cell-free DNA, can be treated as a proxy for the maternal genome alone. The authors state: “the genetic information it contains predominantly reflects the maternal genome” (Page 3) and their entire “NIPT-human-genetics workflow” is built for “genome-wide association analysis of maternal genomes.”

This is a massive oversimplification and a critical error. By treating the mixed signal as purely maternal, the authors are systematically confounding maternal genetic effects with fetal genetic effects in every single analysis, from variant calling to GWAS.

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