Abstract
Secondary findings (SFs) from genome sequencing have significant implications for disease prevention and early intervention, yet their population-specific spectrum remains poorly characterized in non-European cohorts. We performed whole-genome sequencing of 6685 Chinese newborns and evaluated pathogenic variants in 84 genes from the American College of Medical Genetics and Genomics (ACMG) SF v3.3 list according to ACMG/Association for Molecular Pathology (AMP) classification guidelines, and cross-referenced against ClinVar. We identified 306 unique actionable variants, comprising 172 known pathogenic variants (KP) and 134 expected pathogenic variants (EP). When heterozygous carriers of autosomal recessive (AR) variants were included, 9.12% (610/6685) of newborns carried at least one pathogenic variant. Under ACMG SF criteria, clinically actionable variants were identified in 5.06% (338/6685) of newborns, predominantly affecting cardiovascular disease genes (3.49%) and cancer predisposition genes (1.26%), most commonly involving LDLR, TTN, and BRCA2. Importantly, 28 variants across 12 genes showed significant allele frequency divergence between Chinese and European ancestries, highlighting ancestry-specific genetic architecture. Our findings support the inclusion of high-penetrance genes prevalent in East Asian populations in population-tailored genomic screening panels, providing essential reference data for the equitable implementation of precision newborn genomics in underrepresented populations.
Data availability
The data supporting the finding of this study, including the allele frequency for all 399,037 genetic variants across the 84 ACMG-recommended genes, have been deposited in the Genome Variation Map (https://ngdc.cncb.ac.cn/gvm/) at the National Genomics Data Center, China National Center for Bioinformation/Beijing Institute of Genomics, Chinese Academy of Sciences, under the accession number that can be publicly accessible at https://ngdc.cncb.ac.cn/gvm/getProjectDetail?project=GVM001119. The release of the data was approved by the Ministry of Science and Technology of China (Project ID: PRJCA043552). To prevent the disclosure of individuals’ genetic identity, the raw sequencing data and information of the research participants are not publicly available. Further analysis of sequencing data will be made available for collaborating researchers upon request, dependent of the HGRAC’s approval.
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Acknowledgements
We are especially grateful to the participation of the volunteers and their families. We sincerely thank Yuhua Ye for his valuable assistance in the review and interpretation of genetic variants. This work was supported by the National Natural Science Foundation of China (2022YFC2703102), and the China-Serbia Science and Technology Cooperation Committee Exchange Program, Sixth Session (Project 6-3 to M. F.).
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M.F. and X.J. conceived and designed the study. Y.H. performed data analysis, quality control, variant annotation and data interpretation. Y.G., Z.D., X.J., Y.S., and C.L. were responsible for participants recruitment and the collection of samples and associated information. H.H., J.L., S.P., and X.J. contributed to data generation. M.F. and Y.H. drafted the manuscript. M.F., Y.H., and X.J. revised the manuscript. All authors have read and approved the final manuscript.
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Authors Y.H., Y.G., Z.D., H.H., J.L., X.J., and M.F. were employed by Beijing Genomics Institution (BGI) in Shenzhen. The other authors do not have a competing interest.
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Huang, Y., Gao, Y., Duan, Z. et al. Population-scale genomic screening reveals high frequency of actionable secondary findings in Chinese newborns. npj Genom. Med. (2026). https://doi.org/10.1038/s41525-026-00565-0
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DOI: https://doi.org/10.1038/s41525-026-00565-0
