traceCB: Trans-ancestry cell-type-specific eQTLs mapping by integrating scRNA-seq and bulk data

Mapping cell-type-specific expression quantitative trait loci (ct-eQTLs) is essential for interpreting disease-associated variants, yet studies in underrepresented populations are hindered by limited statistical power. Here, we present traceCB, a statistical framework that enhances ct-eQTL mapping in target ancestries by integrating summary statistics from single-cell and bulk-tissue eQTL studies across diverse populations. By explicitly modeling trans-ancestry genetic architecture and accounting for cellular heterogeneity in bulk tissues, traceCB optimizes information borrowing from well-powered European cohorts while robustly controlling for type I error. Simulation studies demonstrate that traceCB achieves superior statistical power compared to original ct-eQTL, particularly when leveraging tissue-level data. In an application to immune cells in East Asian and African cohorts, traceCB increased the effective sample size by up to 2.9-fold and identified approximately 40% more eGenes than single-ancestry analyses, with a replication rate exceeding 90% in independent datasets. Furthermore, traceCB improved the colocalization of regulatory variants with GWAS signals for blood and immune-related traits, revealing cell-type-specific mechanisms underlying complex diseases. These findings establish traceCB as a powerful and scalable tool for leveraging global genomic resources to improve regulatory variant discovery at the cellular level across diverse populations.