Cell-free DNA fragmentomics for preeclampsia risk assessment
Preeclampsia (PE) is a pregnancy-specific hypertensive disorder that could lead to serious maternal and fetal complications, yet early identification of women at risk remains challenging because reliable biomarkers are limited. Here we show that generating relatively stable cell-free DNA (cfDNA) fragmentomic metrics, including transcription start site (TSS) coverage, TSS score, and Gini coefficient, required 600 million whole-genome sequencing reads of plasma cfDNA. These metrics exhibited observable differences among genes with varying expression levels in blood cells and placental tissues. In a cohort of 1,058 pregnant women, cfDNA fragmentomics could distinguish pregnancies that subsequently developed PE. When integrated with maternal risk factors, predictive models in two independent test sets achieved mean area under the curves of 0.903 and 0.850 for early-onset and late-onset PE, respectively, with sensitivities of 0.731 and 0.607 at a 10% false positive rate. Importantly, these models also performed well in samples collected before or at 16 weeks of gestation, supporting the potential of cfDNA fragmentomics in early PE risk assessment.
Authors
- Quanfu Zhang
- Wenzhi Yang (ORCID: https://orcid.org/0000-0003-2780-4853)
- Zhongzhe Li (ORCID: https://orcid.org/0000-0002-9515-1148)
- Xianling Cao (ORCID: https://orcid.org/0000-0001-9544-7419)
- Zhixu Qiu (ORCID: https://orcid.org/0000-0003-1979-5272)
- Yunfang Wang (ORCID: https://orcid.org/0000-0003-2522-3182)
- H Huang
- Huahua Li (ORCID: https://orcid.org/0000-0002-5613-7677)
- Gefei Xiao (ORCID: https://orcid.org/0000-0002-6990-8901)
- Yanning Yin (ORCID: https://orcid.org/0000-0001-7830-6059)
- Suihua Feng
- Sufen Zhang (ORCID: https://orcid.org/0000-0003-4660-3029)
- Weiping Chen (ORCID: https://orcid.org/0000-0001-5658-1914)
- Si Zhou
- Hong Dong (ORCID: https://orcid.org/0000-0002-2604-2597)
- Jie Qin (ORCID: https://orcid.org/0000-0002-5792-5464)
- Dongxia Hou
- Hua Li (ORCID: https://orcid.org/0000-0003-3688-6002)
- Yaxian Liu
- Liqing Hu
- Yan Zhou
- Lijian Zhao
- Xuanyou Zhou
- Naixin Xu
- Zhiguang Zhao
- Xiaohua Wang
- Jianguo Zhang
- Chenming Xu
- Qiang Zhao
- Wuyan Huang
- Cong Liu
- Wenqiu Xu
- Huiqin Li
- Zhen Yang
- Xiao Zhang
- Songchang Chen
- Xiaohong Ruan
- Qun Zhang
- Jie Wang
- Jia Li
Institutions
- BGI Group (China) (CN)
- Hebei Medical University (CN)
- Weihai Maternal and Child Health Hospital (CN)
- Shenzhen Bao'an District People's Hospital (CN)
- Obstetrics and Gynecology Hospital of Fudan University (CN)
- Jiangmen Central Hospital (CN)
- Inner Mongolia Maternal and Child Health (CN)
- Shenzhen Children's Hospital (CN)
- Jiangmen Polytechnic (CN)
- BGI Genomics
Publication Details
- Journal
- Nature Communications
- Published
- 2026-05-02
- DOI
- https://doi.org/10.1038/s41467-026-72682-4
- Primary Topic
- Pregnancy and preeclampsia studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00