Fig. 1: Overview of the study design.
From: cfGWAS reveal genetic basis of cell-free DNA end motifs
A total of 28,016 pregnant women were included in this study, with clinical phenotypes from prenatal care and sequencing data from non-invasive prenatal testing (NIPT) collected. Fragmentation characteristics of cell-free DNA (cfDNA) were extracted from the sequencing data, and after genotype imputation, genotype data were obtained for genome-wide association studies (GWAS). A total of 104 phenotypes and 256 motifs were subjected to GWAS as phenotypic variables, discovering the novel associations of PANX1 and DNASE1L1 genes with the cfDNA end motifs. Experiments with gene knockout (KO) mice and cell lines were conducted to validate these associations. Additionally, a series of post-GWAS analyses was performed by integrating the one-sample 104 phenotypes GWAS results, reported associated loci from the GWAS catalog, and diseases reported in the OMIM database, to explore the biological mechanisms, causal relationship, and gene pleiotropy of cfDNA fragmentation characteristics. The icon of “Public databases” is the official icon of the GWAS catalog database. GWAS Catalog logo is available for re-use under CC-BY-4.0, https://creativecommons.org/licenses/by/4.0/. Created in BioRender. Su, S. (2025) https://BioRender.com/m1tkhdf.
