The blood microbiome map of one million east asian whole-genome sequences from plasma cell-free DNA

Microbial cell-free DNA (mcfDNA) analysis offers a novel approach for monitoring blood-borne viral infections, with prior studies highlighting its clinical utility in viral lineage characterization. However, existing research predominantly employs cross-sectional designs, lacking systematic investigation into spatiotemporal viral dynamics and host genetic regulation. Leveraging non-invasive prenatal testing (NIPT) data from 1,023,651 pregnant women in Hebei Province (2019-2022), we constructed the largest spatiotemporal virome map during pregnancy. Analysis revealed higher viral diversity and load in plain regions compared to mountainous/coastal areas. Temporally, most viruses exhibited annual prevalence increases with winter peaks. Genome-wide association studies (GWAS) identified 4,024 susceptibility loci, potentially modulating immune-related gene expression to influence maternal antiviral immunity. These findings elucidate geographic and genetic influences on viral transmission, demonstrating the value of large-scale NIPT data in infectious disease surveillance. Our study provides critical evidence for establishing pregnancy infection warning systems and precision prevention strategies.