Genetic background of pregnant women can influence result of Non-Invasive Prenatal Test, reports study

A crucial part of NIPT testing revolves around estimating how much of the captured DNA is derived from the placenta. This task is generally performed by an AI algorithm which uses the aforementioned fragmentation properties to predict the proportion of foetal DNA in a plasma sample. This is critical to NIPT as it informs the healthcare professional about the test’s reliability to detect chromosomal abnormalities in the foetus.

"A variant in a gene called DNASE1L3, a molecular pair of scissors that cuts up pieces of DNA into smaller chunks, seems to have the greatest effect, and it is relatively common in the Netherlands – we find it in about 7% of the population. We have found that in people with this variant, the NIPT fails more often because there seems to be less DNA present in the plasma. Even if there is enough DNA available for a test, in these pregnant women the AI algorithms greatly overestimate the amount of DNA that comes from the placenta which can compromise the reliability of their NIPT results,” says Linthorst.

Cell-free DNA is increasingly used as a biomarker in other fields. These findings may therefore also have consequences for the accuracy of those tests, including those currently being developed to test for cancer. "These tests make use of comparable AI prediction models, we've shown here for the first time that these models are affected by genetic background and that may have big consequences for the reliability of other cell-free DNA tests as well,” concludes Sistermans. 

Reference:

Linthorst, Jasper et al., GWAS shows the genetics behind cell-free DNA and highlights the importance of p.Arg206Cys in DNASE1L3 for non-invasive testing, Cell Reports, DOI:10.1016/j.celrep.2024.114799.