Insight into hidden repeatome diversity of Chinese populations

Tandem repeats (TRs) are highly mutable and functionally important genetic elements, yet their genomic diversity, evolutionary dynamics, and medical relevance remain poorly characterized in non-European populations. Here, we reported a high-resolution TR atlas from 21,934 high-coverage genomes, including 17,904 Chinese individuals from 36 ethnolinguistic groups in the GSRD-100KWCH cohort. We identified over three million non-reference TR variants from ~0.7 million polymorphic loci, uncovering population-specific and functionally constrained rare variants that are largely missed from global reference panels. TR-based population analyses resolved fine-scale genetic structures across Chinese populations, including previously underappreciated regional stratifications within Han Chinese and distinctive repeatome profiles associated with geography, language, and demographic features. Leveraging this diverse genomic reservoir, we constructed a deep multi-ancestry haplotype reference panel that substantially enhanced TR imputation accuracy, especially for complex TRs. Furthermore, we demonstrated that natural selection profoundly shapes the human repeatome, with population-differentiated and environment-associated TRs highly enriched in active cis-regulatory elements. Multi-omics quantitative trait locus (QTL) mapping revealed that these potentially adaptive TRs can modulate gene expression and alternative splicing cascades, acting as causal variants driving molecular phenotypes regulation. Notably, adaptive TRs strongly colocalize with genome-wide association study (GWAS) signals, exemplified by a BCL2L11 splicing-associated TR presumably linked to parasite resistance in southern Chinese populations. Our findings reveal hidden repeatome diversity that shaped the adaptive and health trajectories across Chinese populations, providing a foundational resource for advancing precision genomic medicine.